Use of EGFR inhibitor

Abstract

The present invention relates to use of an EGFR inhibitor in the preparation of a medicament for treating an EGFR mutation co-occurring with a deleterious mutation and a method for treating the described disease. Specifically, disclosed is use of a compound of formula I or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating a disease related to an EGFR mutation co-occurring with a deleterious mutation in a subject. The medicament, when administered to a subject with a disease related to an EGFR mutation co-occurring with a deleterious mutation, provides one or more of the following improvements: improved progression-free survival (PFS) or improved overall survival (OS).

Description

Use of an EGFR inhibitor Technical Field The present invention belongs to the field of medicine, and specifically relates to the use of an EGFR inhibitor in preparing a drug for treating EGFR mutations combined with harmful mutations, and a method for treating the above-mentioned diseases. Background Art According to statistics from the National Cancer Center of China, lung cancer ranked first in both incidence and mortality among malignant tumors in China in 2016, with approximately 828,000 new cases and 657,000 deaths (Chinese Medical Association Oncology Branch. Chinese Medical Association Guidelines for Clinical Diagnosis and Treatment of Lung Cancer (2022 Edition) [J]. 2022, 102(23): 1706-1740.). Other data show that in 2020, there were approximately 820,000 newly diagnosed cases of lung cancer and approximately 715,000 deaths in China (Chen P, Liu Y, Wen Y, et al. Non-small cell lung cancer in China [J]. Cancer Commun (Lond). 2022; 42(10): 937-970.). Non-small cell lung cancer (NSCLC) accounts for approximately 85% of primary lung cancers, among which lung adenocarcinoma is the most common pathological subtype of NSCLC. Approximately 50% of lung adenocarcinoma patients in the Chinese population have epidermal growth factor receptor (EGFR) gene mutations (Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII) [J]. Am J Cancer Res. 2015; 5(9): 2892-911.).EGFR gene exon 19 deletion mutation (EGFR 19del) and exon 21 L858R mutation (EGFR L858R) are the most common mutation types (>70%) among EGFR mutations (EGFRm) (Wen S, Dai L, Wang L, et al. Genomic Signature of Driver Genes Identified by Target Next-Generation Sequencing in Chinese Non-Small Cell Lung Cancer[J]. The oncologist. 2019; 24(11): e1070-e1081.), accounting for 40-50% and 30-40% respectively (Kitadai R, Okuma Y. Treatment Strategies for Non-Small Cell Lung Cancer Harboring Common and Uncommon EGFR Mutations: Drug Sensitivity Based on Exon Classification, and Structure-Function Analysis[J].Cancers(Basel).2022;14(10):2519.). EGFRm+ NSCLC is sensitive to EGFR tyrosine kinase inhibitors (TKIs). Multiple clinical studies have demonstrated clear therapeutic benefits from EGFR-TKIs. Currently, several EGFR-TKIs are approved in China for the first-line treatment of patients with advanced NSCLC harboring the EGFR exon 19 or exon 21 L858R mutation. However, EGFRm+ NSCLC patients may have other gene mutations besides EGFR mutations, such as TP53, AKT1, APC, BRAF, CDKN2N, KRAS, KIT, PDGFRA, PIK3CA, STK11, etc. These combined gene mutations may affect the patients' benefit from EGFR-TKIs treatment (Hong S, Gao F, Fu S, Wang Y, Fang W, Huang Y, Zhang L. Concomitant Genetic Alterations With Response to Treatment and Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients With EGFR-Mutant Advanced Non-Small Cell Lung Cancer. JAMA Oncol. 2018 May 1; 4(5): 739-742.). Therefore, how to find a suitable class of targeted drugs to prolong the treatment efficacy of EGFRm+ patients with other gene mutations is an urgent problem that needs to be solved. Summary of the Invention The first aspect of the present invention is to provide a compound having the structure of the following formula I or a pharmaceutically acceptable salt thereof for use in the preparation of a medicament for treating diseases associated with EGFR mutations combined with one or more deleterious mutations: In some embodiments, the pharmaceutically acceptable salt is a conventional salt in the art, such as hydrochloride, phosphate, sulfate, acetate, maleate, methanesulfonate, benzenesulfonate, benzoate, methylbenzenesulfonate, succinate, fumarate, fumarate, tartrate, gallate, and citrate. In some embodiments, the disease is EGFR exon 19 deletion (EGFR 19DEL ) non-small cell lung cancer, or EGFR exon 21 mutation (EGFR L858R ) of non-small cell lung cancer, or the disease is EGFR exon 19 deletion (EGFR 19DEL ) and EGFR exon 21 mutation (EGFR L858R) non-small cell lung cancer, preferably locally advanced or metastatic non-squamous non-small cell lung cancer. In some embodiments, the EGFR mutation is an EGFR exon 19 deletion (EGFR 19DEL ), or EGFR exon 21 mutation (EGFR L858R ), or the disease is EGFR exon 19 deletion and EGFR exon 21 mutation (EGFR L858R ). In some embodiments, the deleterious mutations include at least one of the following gene mutations: ALK, APC, AR, ARID1A, ATM, BRAF, BRCA1, BRCA2, BRIP1, BTK, CDH1, CDKN2A, CHEK2, CTNNB1, ERBB2, ERBB4, ETV6, FANCA, FGFR1, FGFR2, FLT4, FOXL2, GATA3, HNF1A, IDH1, IDH2, KDM6A, KIT, KRAS, M LH1, MPL, MSH6, MTHFR, MUTYH, NBN, NF1, NF2, NFE2L2, NTRK1, PALB2, PDGFRA, PIK3CA, PIK3R1, POLE, PPP2R1A, PTCH 1. PTEN, RAD51C, RAD51D, RAF1, RB1, RET, SF3B1, SMAD4, STK11, TERT, TP53, TSC1, TSC2, TSHR, UGT1A1, VEGFA or VHL; Preferably, The ALK gene mutation is an exon mutation, including exon 3 and / or exon 9 mutations, such as ALK:NM_004304.5:exon3:c.872G>A, ALK:NM_004304.5:exon9:c.1648C>T; The APC gene mutation is an exon mutation, including exon 5 and / or exon 8 and / or exon 12 and / or exon 16 mutations, such as APC:NM_000038.6:exon12:c.1548+1G>A, APC:NM_000038.6:exon16:c.2299C>T, APC:NM_000038.6:exon16:c.2626C>T, APC:NM_000038.6:exon16:c.2926delA, APC:NM_000038.6:exon16:c.2926delA, APC:NM_000038.6:exon16:c.2299C>T, APC:NM_000038.6:exon16:c.2626C>T, APC:NM_000038.6:exon16:c.2926delA, APC:NM_0000 38.6:exon16:c.3688C>T、APC:NM_000038.6:exon16:c.4348C>T、APC:NM_000038.6:exon16:c.4393_4394delAG、APC:N M_000038.6:exon16:c.7932_7935delTTAT, APC:NM_000038.6:exon5:c.481C>T, APC:NM_000038.6:exon8:c.835-8A>G; The AR gene mutation is an exon mutation, including exon 1 and / or exon 6 mutation and / or exon 7 mutation, such as AR:NM_000044.6:exon1:c.902A>G, AR:NM_000044.6:exon6:c.2359C>T, AR:NM_000044.6:exon7:c.2599G>A; The ARID1A gene mutation is an exon mutation, including exon 1 mutation, such as ARID1A:NM_006015.6:exon1:c.175G>T, ARID1A:NM_006015.6:exon1:c.437delC; The ATM gene mutation is an exon mutation, including exon 42 and / or exon 46 mutation and / or exon 49 mutation, such as ATM:NM_000051.3:exon42:c.6100C>T, ATM:NM_000051.3:exon46:c.6807G>A, ATM:NM_000051.3:exon49:c.7141_7151delAATGGAAAAAT, ATM:NM_000051.3:exon49:c.7307G>A, ATM:NM_000051.3:exon5:c.468G>A, ATM:NM_000051.3:exon5:c.496+1G>A, ATM:NM_000051.3:exon50:c.7355T>C, AT M:NM_000051.3:exon51:c.7629+1G>A, ATM:NM_000051.3:exon55:c.8071C>T, ATM:NM_000051.3:exon57:c.8373C>A; The BRAF gene mutation is an exon mutation, including exon 11 mutation, such as BRAF:NM_004333.6:exon11:c.1397G>A; The BRCA1 gene mutation is an exon mutation, including exon 6 mutation and / or exon 10 mutation, such as BRCA1:NM_007294.4:exon10:c.1465G>T, BRCA1:NM_007294.4:exon10:c.2952delT, BRCA1:NM_007294.4:exon10:c.811G>A, BRCA1:NM_007294.4:exon6:c.329dupA; The BRCA2 gene mutation is an exon mutation, including exon 5 and / or exon 7 and / or exon 15 and / or exon 21 mutations, such as BRCA2:NM_000059.3:exon15:c.7522G>A, BRCA2:NM_000059.3:exon21:c.8702G>A, BRCA2:NM_000059.3:exon5:c.475+3A>G, BRCA2:NM_000059.3:exon7:c.631+1G>A; The BRIP1 gene mutation is an exon mutation, including exon 7 and / or exon 8 and / or exon 16 and / or exon 19 mutations, such as BRIP1:NM_032043.3:exon16:c.2324A>G, BRIP1:NM_032043.3:exon19:c.2789C>A, BRIP1:NM_032043.3:exon7:c.632delC, BRIP1:NM_032043.3:exon7:c.918+1G>A, BRIP1:NM_032043.3:exon8:c.1078C>T; The BTK gene mutation is an exon mutation, including exon 15 mutation, such as BTK:NM_000061.2:exon15:c.1455C>A; The CDH1 gene mutation is an exon mutation, including exon 9 mutation, such as CDH1:NM_004360.5:exon9:c.1212delC; The CDKN2A gene mutation is an exon mutation, including exon 1 and / or exon 2 and / or exon 3 and / or exon 4 and / or exon 11 and / or exon 12 and / or exon 13 and / or exon 14 mutations, CDKN2A: NM_000077.4: exon1: c.32dupC, CDKN2A: NM_000077.4: exon2: c.247C>T, CDKN2A: NM_000077.4: exon2: c.387C>A, CHEK2: NM_007194.4: exon11: c .1260-1G>A, CHEK2:NM_007194.4:exon12:c.1355G>A, CHEK2:NM_007194.4:exon13:c.1462-2A>G, CHEK2:NM_007194.4:exon14:c .1482G>C, CHEK2:NM_007194.4:exon3:c.409C>T, CHEK2:NM_007194.4:exon4:c.538C>T, CHEK2:NM_007194.4:exon8:c.876delT; The CTNNB1 gene mutation is an exon mutation, including exon 3 mutations, such as CTNNB1:NM_001904.4:exon3:c.100G>A, CTNNB1:NM_001904.4:exon3:c.101G>A, CTNNB1:NM_001904.4:exon3:c.101G>T, CTNNB1:NM_001904.4:exon3:c.110C>A, CTNNB1:NM_001904.4:exon3:c.110C>G, CTNNB1:NM_001904.4:exon3:c.110C>T, CTNNB1:NM_001904.4:exon3:c.110C>T, CTNNB1:NM_001904.4:exon3:c.110C>T, CTNNB1:NM_001904.4:exon3:c.110C>A, CTNNB1:NM_001904.4:exon3:c.110C>G, CTNNB1:NM_001904.4:exon3:c.110C>T, CTNNB1:NM_001904.4:exon3:c.110C>T, xon3:c.122C>T、CTNNB1:NM_001904.4:exon3:c.133_135delTCT、CTNNB1:NM_001904.4:exon3:c.133T>C、CTNNB1:NM_001904.4:exon3:c.94G>A、CTNNB 1:NM_001904.4:exon3:c.94G>C, CTNNB1:NM_001904.4:exon3:c.94G>T:, CTNNB1:NM_001904.4:exon3:c.98C>G, CTNNB1:NM_001904.4:exon3:c.98C>T; The ERBB2 gene mutation is an exon mutation, including exon 8 mutation, such as ERBB2:NM_004448.3:exon8:c.929C>T; The ERBB4 gene mutation is an exon mutation, including exon 2 mutation, such as ERBB4:NM_005235.3:exon2:c.119_120delCT; The ETV6 gene mutation is an exon mutation, including exon 7 mutation, such as ETV6:NM_001987.5:exon7:c.1195C>T; The FANCA gene mutation is an exon mutation, including exon 39 mutation, such as FANCA:NM_000135.4:exon39:c.3906G>A; The FGFR1 gene mutation is an exon mutation, including exon 4 mutation, such as FGFR1:NM_023110.3:exon4:c.448+1G>A; The FGFR2 gene mutation is an exon mutation, including exon 8 mutation, such as FGFR2:NM_000141.4:exon8:c.1075G>A; The FLT4 gene mutation is an exon mutation, including exon 23 mutation, such as FLT4:NM_182925.5:exon23:c.3121C>T; The FOXL24 gene mutation is an exon mutation, including exon 1 mutation, such as FOXL2:NM_023067.4:exon1:c.1045C>G; The GATA3 gene mutation is an exon mutation, including exon 3 mutation, such as GATA3:NM_001002295.2:exon3:c.431delG; The HNF1A gene mutation is an exon mutation, including exon 6 mutation, such as HNF1A:NM_000545.6:exon6:c.1129delC; The IDH1 gene mutation is an exon mutation, including exon 4 mutation, such as IDH1:NM_005896.3:exon4:c.394C>T; The IDH2 gene mutation is an exon mutation, including a 4-exon mutation, such as IDH2:NM_002168.3:exon4:c.419G>A; The KDM6A gene mutation is an exon mutation, including exon 18 mutation, such as KDM6A:NM_001291415.1:exon18:c.2858+1G>A; The KIT gene mutation is an exon mutation, including exon 5 mutation, such as KIT:NM_000222.2:exon5:c.910A>G; The KRAS gene mutation is an exon mutation, including exon 2 mutation, such as KRAS:NM_004985.5:exon2:c.38G>A; The MLH1 gene mutation is an exon mutation, including exon 10 mutation, such as MLH1:NM_000249.3:exon10:c.793C>T; The MPL gene mutation is an exon mutation, including exon 3 mutation, such as MPL:NM_005373.3:exon3:c.235_236delCT; The MSH6 gene mutation is an exon mutation, including exon 4 mutation, such as MSH6:NM_000179.2:exon4:c.2927G>A; The MTHFR gene mutation is an exon mutation, including exon 5 mutation, such as MTHFR:NM_005957.5:exon5:c.680C>T; The MUTYH gene mutation is an exon mutation, including exon 10 and / or exon 13 mutations, such as MUTYH:NM_001128425.1:exon10:c.934-2A>G, MUTYH:NM_001128425.1:exon13:c.1187G>A; The NBN gene mutation is an exon mutation, including exon 1 mutation, such as NBN:NM_002485.4:exon1:c.3G>A; The NF1 gene mutation is an exon mutation, including exon 5 and / or exon 9 and / or exon 12 and / or exon 23 and / or exon 25 and / or exon 33 and / or exon 34 and / or exon 38 mutations, such as NF1:NM_001042492.3:exon12:c.1381C>T, NF1:NM_001042492.3:exon23:c.3113G>C:, NF1:NM_001042492.3:exon25:c.3315-1G>T, NF1:NM_001042492.3:exon34:c.3326-1G>T, NF1:NM_001042492.3:exon35:c.3337-1G>T, NF1:NM_001042492.3:exon36:c.3340-1G>T, NF1:NM_001042492.3:exon37:c.3341-1G>T, NF1:NM_001042492.3:exon38:c.3342-1G>T, NF1:NM_001042492.3:exon39:c.3433-1G>T, NF1:NM_001042492.3:exon40:c.3434-1G>T, NF1:NM_001042492.3:exon41:c.3435-1G>T, NF1:NM_001042492.3:exon42:c.3436-1G>T, NF1:N 001042492.3:exon33:c.4339C>G, NF1:NM_001042492.3:exon33:c.4339C>T, NF1:NM_001042492.3:exon34:c.4498A>G, NF1 :NM_001042492.3:exon38:c.5609G>A, NF1:NM_001042492.3:exon5:c.484C>T, NF1:NM_001042492.3:exon9:c.1062+1G>A; The NF2 gene mutation is an exon mutation, including exon 13 mutation, such as NF2:NM_000268.3:exon13:c.1396C>T; The NFE2L2 gene mutation is an exon mutation, including exon 2 mutation, such as NFE2L2:NM_006164.5:exon2:c.85G>C; The NTRK1 gene mutation is an exon mutation, including exon 14 and / or exon 15 and / or exon 17 mutations, such as NTRK1:NM_002529.3:exon14:c.1768G>A, NTRK1:NM_002529.3:exon15:c.1945C>T, NTRK1:NM_002529.3:exon17:c.2303C>T; The PALB2 gene mutation is an exon mutation, including exon 4 and / or exon 5 mutations, such as PALB2:NM_024675.4:exon4:c.1213C>G, PALB2:NM_024675.4:exon4:c.1546delA, PALB2:NM_024675.4:exon5:c.2038G>T; The PDGFRA gene mutation is an exon mutation, including exon 11 and / or exon 22 mutations, such as PDGFRA:NM_006206.6:exon11:c.1631T>C, PDGFRA:NM_006206.6:exon22:c.2942G>A, PDGFRA:NM_006206.6:exon22:c.3098A>T; The PIK3CA gene mutation is an exon mutation, including exon 2 and / or exon 5 and / or exon 8 and / or exon 10 and / or exon 19 and / or exon 21 mutations, such as PIK3CA:NM_006218.4:exon10:c.1624G>A, PIK3CA:NM_006218.4:exon10:c.1624G>C, PIK3CA:NM_006218.4:exon10:c.1633G>A:, PIK3CA:NM_006218.4:exon10:c.1637A>G, PIK3CA:NM_0062 18.4:exon19:c.2702G>T, PIK3CA:NM_006218.4:exon2:c.323G>A, PIK3CA:NM_006218.4:exon21:c.3129G>T, PIK3CA:NM_006218.4:exon21 ; The PIK3R1 gene mutation is an exon mutation, including exon 11 mutation, such as PIK3R1:NM_181523.3:exon11:c.1425+1G>A; The POLE gene mutation is an exon mutation, including exon 5 and / or exon 13 mutations, such as POLE:NM_006231.4:exon13:c.1270C>G, POLE:NM_006231.4:exon5:c.424-1G>A; The PPP2R1A gene mutation is an exon mutation, including exon 5 and / or exon 6 mutations, such as PPP2R1A:NM_014225.6:exon5:c.544C>T, PPP2R1A:NM_014225.6:exon6:c.656C>T; The PTCH1 gene mutation is an exon mutation, including exon 14 mutation, such as PTCH1:NM_000264.5:exon14:c.2178dupC; The PTEN gene mutation is an exon mutation, including exon 2 and / or exon 3 and / or exon 5 and / or exon 6 mutations, including exon 8 and / or exon 9 mutations, such as PTEN: NM_000314.8: exon2: c.107G>A, PTEN: NM_000314.8: exon3: c.209+5G>A, PTEN: NM_000314.8: exon5: c.403A>G, PTEN: NM_000314.8: exon5: c.464A>G, PTEN EN:NM_000314.8:exon6:c.511C>G, PTEN:NM_000314.8:exon6:c.518G>C, PTEN:NM_000314.8:exon6:c.593T>A, PTEN:NM _000314.8:exon8:c.1026+1G>T, PTEN:NM_000314.8:exon8:c.955_958delACTT, PTEN:NM_000314.8:exon9:c.1211G>C; The RAD51C gene mutation is an exon mutation, including exon 4 and / or exon 5 mutations, such as RAD51C:NM_058216.3:exon5:c.709C>T, RAD51D:NM_002878.3:exon4:c.345+1G>A; The RAF1 gene mutation is an exon mutation, including exon 7 mutation, such as RAF1:NM_002880.3:exon7:c.770C>T; The RB1 gene mutation is an exon mutation, including exon 2 and / or exon 8 and / or exon 14 and / or exon 19 and / or exon 20 and / or exon 21 and / or exon 22 and / or exon 23 mutations, such as RB1:NM_000321.2:exon13:c.1332+1G>A, RB1:NM_000321.2:exon14:c.1346dupG, RB1:NM_000321.2:exon19:c.1960+1G>T, RB1:NM_000321.2:exon2 :c.142G>T, RB1:NM_000321.2:exon2:c.219_220delAG, RB1:NM_000321.2:exon20:c.2107-1G>C, RB1:NM_000321.2:exon21:c.2 211+5G>A, RB1:NM_000321.2:exon22:c.2325+1G>A, RB1:NM_000321.2:exon23:c.2359C>T, RB1:NM_000321.2:exon8:c.751C>T; The RET gene mutation is an exon mutation, including exon 3 mutation, such as RET:NM_020975.6:exon3:c.433G>A; The SF3B1 gene mutation is an exon mutation, including exon 14 mutation, such as SF3B1:NM_012433.3:exon14:c.1998G>C; The SMAD4 gene mutation is an exon mutation, including exon 6 and / or exon 9 and / or exon 10 and / or exon 12 mutations, such as SMAD4:NM_005359.6:exon10:c.1156G>A, SMAD4:NM_005359.6:exon12:c.1612G>T, SMAD4:NM_005359.6:exon6:c.692delG, SMAD4:NM_005359.6:exon9:c.1081C>A, SMAD4:NM_005359.6:exon9:c.1081C>T, SMAD4:NM_005359.6:exon9:c.1082G>A; The STK11 gene mutation is an exon mutation, including exon 1 and / or exon 8 mutations, such as STK11:NM_000455.5:exon1:c.291-2A>G, STK11:NM_000455.5:exon8:c.923G>A; The TERT gene mutation is a non-coding region mutation, such as TERT:NM_198253.3:exon-:c.-124C>T; The TP53 gene mutation is an exon mutation, including exon 3 and / or exon 4 and / or exon 5 and / or exon 6 and / or exon 7 and / or exon 8 and / or exon 9 and / or exon 10 mutations, such as TP53:NM_000546.5:exon10:c.1009C>T, TP53:NM_000546.5:exon10:c.1010G>A, TP53:NM_000546.5:exon10:c.1024C>T, TP53:NM_000546.5:exon3:c.80delC, TP53:NM_000546.5:exon3:c.97 -1G>A, TP53:NM_000546.5:exon3:c.97-2delA, TP53:NM_000546.5:exon4:c.102delC, TP53:NM_000546.5:exon4:c.154C>T, TP53:NM_000546.5:ex on4:c.159G>A, TP53:NM_000546.5:exon4:c.216dupC, TP53:NM_000546.5:exon4:c.281C>A, TP53:NM_000546.5:exon4:c.298C>T, TP53:NM_000546 .5:exon4:c.310C>T、TP53:NM_000546.5:exon4:c.329G>T、TP53:NM_000546.5:exon4:c.337T>G、TP53:NM_000546.5:exon4:c.374C>T、TP53:NM_00 0546.5:exon4:c.375+1G>T、TP53:NM_000546.5:exon4:c.376-1G>A、TP53:NM_000546.5:exon5:c.388C>T、TP53:NM_000546.5:exon5:c.389T>A:、T P53:NM_000546.5:exon5:c.398T>C, TP53:NM_000546.5:exon5:c.403T>C, TP53:NM_000546.5:exon5:c.404G>A, TP53:NM_000546.5:exon5:c.404G >T, TP53:NM_000546.5:exon5:c.413C>T, TP53:NM_000546.5:exon5:c.421T>C, TP53:NM_000546.5:exon5:c.422G>A, TP53:NM_000546.5:exon5:c.430C>T、TP53:NM_000546.5:exon5:c.451C>T、TP53:NM_000546.5:exon5:c.455C>G、TP53:NM_000546.5:exon5:c.455C>T:、TP53:NM_000546.5:exon5:c.464C>A、TP53:NM_000546.5:exon5:c.469G>T、TP53:NM_000546.5:exon5:c.473G>T、TP53:NM_000546.5:exon5:c.481G>A、TP53:NM_000546.5:exon5:c.493C>T、TP53:NM_000546.5:exon5:c.499C>T、TP53:NM_000546.5:exon5:c.503A>G、TP53:NM_000546.5:exon5:c.517G>T、TP53:NM_000546.5:exon5:c.518T>C、TP53:NM_000546.5:exon5:c.523C>G、TP53:NM_000546.5:exon5:c.524G>A、TP53:NM_000546.5:exon5:c.524G>T、TP53:NM_000546.5:exon5:c.527G>A、TP53:NM_000546.5:exon5:c.527G>T、TP53:NM_000546.5:exon5:c.532delC、TP53:NM_000546.5:exon5:c.535C>G:、TP53:NM_000546.5:exon5:c.538G>A、TP53:NM_000546.5:exon5:c.541C>T、TP53:NM_000546.5:exon6:c.577C>T、TP53:NM_000546.5:exon6:c.578A>G、TP53:NM_000546.5:exon6:c.615T>A、TP53:NM_000546.5:exon6:c.626_627delGA、TP53:NM_000546.5:exon6:c.637C>T、TP53:NM_000546.5:exon6:c.638G>A、TP53:NM_000546.5:exon6:c.638G>C、TP53:NM_000546.5:exon6:c.641A>G、TP53:NM_000546.5:exon6:c.644G>T、TP53:NM_000546.5:exon6:c.646G>A、TP53:NM_000546.5:exon6:c.646G>T、TP53:NM_000546.5:exon6:c.659A>G、TP53:NM_000546.5:exon6:c.661G>T、TP53:NM_000546.5:exon6:c.673-1G>T、TP53:NM_000546.5:exon7:c.701A>G、TP53:NM_000546.5:exon7:c.707A>G、TP53:NM_000546.5:exon7:c.718A>C、TP53:NM_000546.5:exon7:c.718A>G、TP53:NM_000546.5:exon7:c.722C>T、TP53:NM_000546.5:exon7:c.725G>T、TP53:NM_000546.5:exon7:c.730G>A、TP53:NM_000546.5:exon7:c.730G>T、TP53:NM_000546.5:exon7:c.733G>A、TP53:NM_000546.5:exon7:c.734G>A、TP53:NM_000546.5:exon7:c.734G>T、TP53:NM_000546.5:exon7:c.737T>A:、TP53:NM_000546.5:exon7:c.742C>G、TP53:NM_000546.5:exon7:c.742C>T、TP53:NM_000546.5:exon7:c.743G>A、TP53:NM_000546.5:exon7:c.743G>T、TP53:NM_000546.5:exon7:c.745A>T、TP53:NM_000546.5:exon7:c.746G>A、TP53:NM_000546.5:exon7:c.761T>C、TP53:NM_000546.5:exon7:c.776A>T、TP53:NM_000546.5:exon7:c.782+1G>A、TP53:NM_000546.5:exon7:c.783-1G>T、TP53:NM_000546.5:exon7:c.783-2A>C、TP53:NM_000546.5:exon8:c.797G>T、TP53:NM_000546.5:exon8:c.811G>A、TP53:NM_000546.5:exon8:c.814G>A、TP53:NM_000546.5:exon8:c.814G>T, TP53:NM_000546.5:exon8:c.817C>T, TP53:NM_000546.5:exon8:c.818G>A:, TP53:NM_000546.5:exon8 :c.818G>C:, TP53:NM_000546.5:exon8:c.823T>C, TP53:NM_000546.5:exon8:c.830G>T, TP53:NM_000546.5:exo n8:c.832C>A, TP53:NM_000546.5:exon8:c.833C>T, TP53:NM_000546.5:exon8:c.836G>A, TP53:NM_000546.5:e xon8:c.839G>C、TP53:NM_000546.5:exon8:c.841G>C、TP53:NM_000546.5:exon8:c.844C>G、TP53:NM_000546.5: exon8:c.844C>T, TP53:NM_000546.5:exon8:c.848G>C, TP53:NM_000546.5:exon8:c.853G>A, TP53:NM_000546. 5:exon8:c.856G>A, TP53:NM_000546.5:exon8:c.919+2T>A, TP53:NM_000546.5:exon8:c.920-2A>G, TP53:NM_00 0546.5:exon9:c.927delC, TP53:NM_000546.5:exon9:c.949C>T, TP53:NM_000546.5:exon9:c.988delC, TP53:N M_000546.5:exon9:c.991C>T, TP53:NM_000546.5:exon9:c.993+1G>T, TP53:NM_000546.5:exon9:c.994-1G>A;. The TSC1 gene mutation is an exon mutation, including exon 15 and / or exon 17 and / or exon 18 mutations, such as TSC1:NM_000368.5:exon15:c.1498C>T, TSC1:NM_000368.5:exon17:c.2074C>T, TSC1:NM_000368.5:exon18:c.2227C>T; The TSC2 gene mutation is an exon mutation, including exon 11 and / or exon 21 and / or exon 22 mutations, such as TSC2:NM_000548.5:exon11:c.1111C>T, TSC2:NM_000548.5:exon21:c.2355+1G>A, TSC2:NM_000548.5:exon22:c.2365G>A; The TSHR gene mutation is an exon mutation, including exon 10 mutation, such as TSHR:NM_000369.3:exon10:c.1349G>A, TSHR:NM_000369.3:exon10:c.1574T>C; The UGT1A1 gene mutation is an exon mutation, including exon 1 mutation, such as UGT1A1:NM_000463.3:exon1:c.686C>A; The VEGFA gene mutation is an exon mutation, including exon 1 mutation, such as VEGFA:NM_001025366.3:exon1:c.19_22dupGACA; The VHL gene mutation is an exon mutation, including exon 3 mutation, such as VHL:NM_000551.3:exon3:c.482G>A; Preferably, The ALK amino acid mutation is a missense mutation, including missense mutations at amino acid position 291 and / or amino acid position 550, such as ALK:NM_004304.5:p.Arg291His:p.R291H, ALK:NM_004304.5:p.Leu550Phe:p.L550F; The APC amino acid mutation is a frameshift mutation and / or a non-coding region mutation and / or a nonsense mutation and / or a splice site mutation, including an amino acid nonsense mutation at position 161 and / or an amino acid nonsense mutation at position 1450 and / or an amino acid frameshift mutation at position 1465 and / or an amino acid nonsense mutation at position 1230 and / or an amino acid nonsense mutation at position 767 and / or an amino acid nonsense mutation at position 876 and / or an amino acid frameshift mutation at position 976 and / or an amino acid frameshift mutation at position 2645 and / or a non-coding region mutation and / or a splice site mutation, for example, APC:NM_000038.6:p.Gln767*:p.Q767X, APC:NM_000038.6:p.Arg 876*:p.R876X, APC:NM_000038.6:p.Arg976fs:p.R976Efs*4, APC:NM_000038.6:p.Gln1230*:p.Q1230X, APC:NM_000038.6:p.Arg1450*:p.R14 50X, APC:NM_000038.6:p.Ser1465fs:p.S1465Wfs*3, APC:NM_000038.6:p.Tyr2645fs:p.Y2645Kfs*14, APC:NM_000038.6:p.Gln161*:p.Q161X; The AR amino acid mutation is a nonsense mutation and / or a missense mutation, including a missense mutation at amino acid position 301 and / or a nonsense mutation at amino acid position 787 and / or a missense mutation at amino acid position 867, for example, AR:NM_000044.6:p.Lys301Arg:p.K301R, AR:NM_000044.6:p.Arg787*:p.R787X, AR:NM_000044.6:p.Val867Met:p.V867M; The ARID1A amino acid mutation is a nonsense mutation and / or a frameshift mutation, including a nonsense mutation at position 59 and / or a frameshift mutation at position 146, such as ARID1A:NM_006015.6:p.Glu59*:p.E59X, ARID1A:NM_006015.6:p.Pro146fs:p.P146Qfs*86; The ATM amino acid mutation is a splice site mutation and / or a nonsense mutation and / or a missense mutation and / or a frameshift mutation and / or a synonymous mutation, including a nonsense mutation at amino acid position 2034 and / or a missense mutation at amino acid position 2436 and / or a frameshift mutation at amino acid position 2381 and / or a nonsense mutation at amino acid position 156 and / or a synonymous mutation at amino acid position 2269 and / or a missense mutation at amino acid position 2452 and amino acid position 2691 and / or a nonsense mutation at amino acid position 2791 and / or a splice site mutation, for example, ATM:NM_000051.3:p.Arg2034*:p.R2034X, ATM:NM_000051.3:p.G ln2269Gln:p.Q2269Q、ATM:NM_000051.3:p.Asn2381fs:p.N2381Efs*18、ATM:NM_000051.3:p.Arg2436Lys:p.R2436K、ATM:NM_000051.3:p .Trp156*:p.W156X, ATM:NM_000051.3:p.Leu2452Pro:p.L2452P, ATM:NM_000051.3:p.R2691C, ATM:NM_000051.3:p.Tyr2791*:p.Y2791X; The BRAF amino acid mutation is a missense mutation, including a missense mutation at amino acid position 466, such as BRAF:NM_004333.6:p.Gly466Glu:p.G466E; The BRCA1 amino acid mutation is a missense mutation and / or a frameshift mutation and / or a nonsense mutation, including an amino acid frameshift mutation at position 111 and / or an amino acid missense mutation at position 271 and / or an amino acid nonsense mutation at position 489 and / or an amino acid frameshift mutation at position 986, for example, BRCA1:NM_007294.4:p.Glu489*:p.E489X, BRCA1:NM_007294.4:p.Ile986fs:p.I986Sfs*14, BRCA1:NM_007294.4:p.Val271Met:p.V271M, BRCA1:NM_007294.4:p.Glu111fs:p.E111Gfs*3; The BRCA2 amino acid mutation is a missense mutation and / or a non-coding region mutation, including a missense mutation at amino acid position 2508 and / or a missense mutation at amino acid position 2901; for example, BRCA2: NM_000059.3: p.Gly2508Ser: p.G2508S, BRCA2: NM_000059.3: p.Gly2901Asp: p.G2901D; The BRIP1 amino acid mutation is a splice site mutation and / or a nonsense mutation and / or a frameshift mutation and / or a missense mutation, including a nonsense mutation at amino acid position 360 and / or a nonsense mutation at amino acid position 930 and / or a frameshift mutation at amino acid position 211 and / or a missense mutation at amino acid position 775 and / or a splice site mutation, for example, BRIP1:NM_032043.3:p.Asn775Ser:p.N775S, BRIP1:NM_032043.3:p.Ser930*:p.S930X, BRIP1:NM_032043.3:p.Pro211fs:p.P211Lfs*63, BRIP1:NM_032043.3:p.Gln360*:p.Q360X; The BTK amino acid mutation is a nonsense mutation, including a nonsense mutation at amino acid position 485, such as BTK:NM_000061.2:p.Tyr485*:p.Y485X; The CDH1 amino acid mutation is a frameshift mutation, including a frameshift mutation at amino acid position 405, such as CDH1:NM_004360.5:p.Asn405fs:p.N405Ifs*12; The CDKN2A amino acid mutation is a missense mutation and / or a frameshift mutation and / or a nonsense mutation, including a missense mutation at amino acid position 83 and / or a frameshift mutation at amino acid position 12 and / or a nonsense mutation at amino acid position 129, for example, CDKN2A:NM_000077.4:p.Ser12fs:p.S12Ffs*3, CDKN2A:NM_000077.4:p.His83Tyr:p.H83Y, CDKN2A:NM_000077.4:p.Tyr129*:p.Y129X; The CHEK2 amino acid mutation is a splice site mutation and / or a frameshift mutation and / or a missense mutation and / or a nonsense mutation, including a frameshift mutation at amino acid position 292 and / or a missense mutation at amino acid position 494 and / or a nonsense mutation at amino acid position 452 and / or a nonsense mutation at amino acid position 137 and / or a missense mutation at amino acid position 180 and / or a splice site mutation, for example, CHEK2: NM_007194.4: p.Trp452*: p.W 452X, CHEK2:NM_007194.4:p.Lys494Asn:p.K494N, CHEK2:NM_007194.4:p.Arg137*:p.R137X, CHEK2:NM_007194.4:p.Arg180Cys:p.R180C, CHEK2:NM_007194.4:p.Phe292fs:p.F292Lfs*12; The CTNNB1 amino acid mutation is a missense mutation and / or an indel in the non-heritage coding region, for example, a missense mutation at amino acid position 37 and / or a missense mutation at amino acid position 41 and / or an indel in the non-heritage coding region at amino acid position 45 and / or a missense mutation at amino acid position 45 and / or a missense mutation at amino acid position 33 and / or a missense mutation at amino acid position 37 and / or a missense mutation at amino acid position 34 and / or a missense mutation at amino acid position 32, for example, CTNNB1: NM_001904.4 :p.Gly34Arg:p.G34R、CTNNB1:NM_001904.4:p.Gly34Glu:p.G34E、CTNNB1:NM_001904.4:p.Gly34V al:p.G34V、CTNNB1:NM_001904.4:p.Ser37Tyr:p.S37Y、CTNNB1:NM_001904.4:p.Ser37Cys:p.S37C、 CTNNB1:NM_001904.4:p.Ser37Phe:p.S37F、CTNNB1:NM_001904.4:p.Thr41Ile:p.T41I、CTNNB1:NM _001904.4:p.Ser45del:p.S45del、CTNNB1:NM_001904.4:.Ser45Pro:p.S45P、CTNNB1:NM_001904.4 :p.Asp32Asn:p.D32N、CTNNB1:NM_001904.4:p.Asp32His:p.D32H、CTNNB1:NM_001904.4:p.Asp32T yr:p.D32Y, CTNNB1:NM_001904.4:p.Ser33Cys:p.S33C, CTNNB1:NM_001904.4:p.Ser33Phe:p.S33F; The ERBB2 amino acid mutation is a missense mutation, including a missense mutation at amino acid position 310, such as ERBB2:NM_004448.3:p.Ser310Phe:p.S310F; The ERBB4 amino acid mutation is a frameshift mutation, including a frameshift mutation at amino acid position 40, such as ERBB4:NM_005235.3:p.Ser40fs:p.S40*; The ETV6 amino acid mutation is a missense mutation, including a missense mutation at amino acid position 399, such as ETV6:NM_001987.5:p.Arg399Cys:p.R399C; The FANCA amino acid is a nonsense mutation, including a nonsense mutation at amino acid position 1302, such as FANCA:NM_000135.4:p.Trp1302*:p.W1302X; The FLT4 amino acid mutation is a missense mutation, including a missense mutation at amino acid position 1041, such as FLT4:NM_182925.5:p.Arg1041Trp:p.R1041W; The FOXL2 amino acid mutation is a missense mutation, including a missense mutation at amino acid position 349, such as FOXL2:NM_023067.4:p.Arg349Gly:p.R349G; The GATA3 amino acid mutation is a frameshift mutation, including a frameshift mutation at amino acid position 144, such as GATA3:NM_001002295.2:p.Gly144fs:p.G144Afs*51; The HNF1A amino acid mutation is a frameshift mutation, including a frameshift mutation at amino acid position 377, such as HNF1A:NM_000545.6:p.Leu377fs:p.L377Sfs*7; The IDH1 amino acid mutation is a missense mutation, including a missense mutation at amino acid position 132, such as IDH1:NM_005896.3:p.Arg132Cys:p.R132C; The IDH2 amino acid mutation is a missense mutation, including a missense mutation at amino acid position 140, such as IDH2:NM_002168.3:p.Arg140Gln:p.R140Q; The KIT amino acid mutation is a missense mutation, including a missense mutation at amino acid position 304, such as KIT:NM_000222.2:p.Thr304Ala:p.T304A; The KRAS amino acid mutation is a missense mutation, including a missense mutation at amino acid position 13, such as KRAS:NM_004985.5:p.Gly13Asp:p.G13D; The MLH1 amino acid mutation is a missense mutation, including a missense mutation at amino acid position 265, such as MLH1:NM_000249.3:p.Arg265Cys:p.R265C; The MPL amino acid mutation is a frameshift mutation, including a frameshift mutation at amino acid position 79, such as MPL:NM_005373.3:p.Leu79fs:p.L79Efs*84; The MSH6 amino acid mutation is a missense mutation, including a missense mutation at amino acid position 976, such as MSH6:NM_000179.2:p.Arg976His:p.R976H; The MTHFR amino acid mutation is a missense mutation, including a missense mutation at amino acid position 227, such as MTHFR:NM_005957.5:p.Thr227Met:p.T227M; The MUTYH amino acid mutation is a missense mutation and / or a splice site mutation, including a missense mutation and / or a splice site mutation at amino acid position 396, for example, MUTYH:NM_001128425.1:p.Gly396Asp:p.G396D; The NBN amino acid mutation is a start codon deletion mutation, including a first amino acid start codon deletion mutation, such as NBN:NM_002485.4:p.Met1:p.M1; The NF1 amino acid mutation is a missense mutation and / or a splice site mutation and / or a nonsense mutation, including a missense mutation at position 5100 and / or a missense mutation at position 1870 and / or a nonsense mutation at position 461 and / or a nonsense mutation at position 162 and / or a nonsense mutation at position 1447 and / or a missense mutation at position 1038 and / or a splice site mutation, for example, NF1:NM_001042492.3:p.Arg461*:p.R461X, NF1:NM_001042492.3:p.Arg1038Thr:p .R1038T, NF1:NM_001042492.3:p.Gln1447Glu:p.Q1447E, NF1:NM_001042492.3:p.Gln1447*:p.Q1447X, NF1:NM_00104249 2.3:p.Ser1500Gly:p.S1500G, NF1:NM_001042492.3:p.Arg1870Gln:p.R1870Q, NF1:NM_001042492.3:p.Gln162*:p.Q162X; The NF2 amino acid mutation is a nonsense mutation, including a nonsense mutation at amino acid position 466, such as NF2:NM_000268.3:p.Arg466*:p.R466X; The NFE2L2 amino acid mutation is a missense mutation, including a missense mutation at amino acid position 29, such as NFE2L2:NM_006164.5:p.Asp29His:p.D29H; The NTRK1 amino acid mutation is a missense mutation, including a missense mutation at amino acid position 649 and / or a missense mutation at amino acid position 590 and / or a missense mutation at amino acid position 768, such as NTRK1:NM_002529.3:p.Glu590Lys:p.E590K, NTRK1:NM_002529.3:p.Arg649Trp:p.R649W, NTRK1:NM_002529.3:p.Pro768Leu:p.P768L; The PALB2 amino acid mutation is a missense mutation and / or a nonsense mutation and / or a frameshift mutation, including a missense mutation at amino acid position 405 and / or a nonsense mutation at amino acid position 680 and / or a frameshift mutation at amino acid position 516, for example, PALB2:NM_024675.4:p.Pro405Ala:p.P405A, PALB2:NM_024675.4:p.Arg516fs:p.R516Efs*45, PALB2:NM_024675.4:p.Gly680*:p.G680X; The PDGFRA amino acid mutation is a missense mutation, including a missense mutation at amino acid position 1033 and / or a missense mutation at amino acid position 544 and / or a missense mutation at amino acid position 981, such as PDGFRA:NM_006206.6:p.Val544Ala:p.V544A, PDGFRA:NM_006206.6:p.Arg981His:p.R981H, PDGFRA:NM_006206.6:p.Asp1033Val:p.D1033V; The PIK3CA amino acid mutation is a missense mutation and / or a splice site mutation, including a missense mutation at position 545 and / or a missense mutation at position 1047 and / or a missense mutation at position 344 and / or a missense mutation at position 108 and / or a missense mutation at position 1043 and / or a missense mutation at position 546 and / or a missense mutation at position 542 and / or a missense mutation at position 543 and / or 901 amino acid missense mutation and / or splice site mutation, such as PIK3CA:NM_006218.4:p.Glu542Lys:p.E542K, PIK3CA:NM_006218.4:p.Glu542Gln:p.E542Q, PIK3CA:NM_006218.4:p.Glu545Lys:p.E545K, PIK3CA:NM_006218.4:p.Glu546Lys:p.E546K, 218.4:p.Gln546Arg:p.Q546R、PIK3CA:NM_006218.4:p.Cys901Phe:p.C901F、PIK3CA:NM_0 06218.4:p.Arg108His:p.R108H、PIK3CA:NM_006218.4:p.Met1043Ile:p.M1043I、PIK3CA: NM_006218.4:p.His1047Arg:p.H1047R、PIK3CA:NM_006218.4:p.His1047Leu:p.H1047L、P IK3CA:NM_006218.4:p.Val344Met:p.V344M, PIK3CA:NM_006218.4:p.Glu453Gln:p.E453Q; The POLE amino acid mutation is a missense mutation, including a missense mutation at amino acid position 424, such as POLE:NM_006231.4:p.Leu424Val:p.L424V; The PPP2R1A amino acid mutation is a missense mutation, including a missense mutation at amino acid position 189 and / or a missense mutation at amino acid position 219, such as PPP2R1A:NM_014225.6:p.Arg182Trp:p.R182W, PPP2R1A:NM_014225.6:p.Ser219Leu:p.S219L; The PTCH1 amino acid mutation is a frameshift mutation, including a frameshift mutation at amino acid position 727, such as PTCH1:NM_000264.5:p.Cys727fs:p.C727Lfs*11; The PTEN amino acid mutation is a missense mutation and / or a splice site mutation and / or a frameshift mutation and / or a stop codon mutation and / or a non-coding region mutation, including a missense mutation at amino acid position 198 and / or a missense mutation at amino acid position 135 and / or a frameshift mutation at amino acid position 319 and / or a missense mutation at amino acid position 171 and / or a stop codon deletion at amino acid position 404 and / or a missense mutation at amino acid position 36 and / or a missense mutation at amino acid position 155 and / or a missense mutation at amino acid position 173, for example, PTEN: NM_000314.8: p.Gly36Glu: p.G36E, PTEN: NM_000314.8: p.Ile135V al:p.I135V, PTEN:NM_000314.8:p.Tyr155Cys:p.Y155C, PTEN:NM_000314.8:p.Gln171Glu:p.Q171E, PTEN:NM_000314.8:p.Arg173Pro:p.R1 73P, PTEN:NM_000314.8:p.Met198Lys:p.M198K, PTEN:NM_000314.8:p.Thr319fs:p.T319*, PTEN:NM_000314.8:p.Ter404Serext*:p.X404S; The RAD51C amino acid mutation is a nonsense mutation, including a nonsense mutation at amino acid position 237, such as RAD51C:NM_058216.3:p.Arg237*:p.R237X; The RAD51D amino acid mutation is a splice site mutation; The RAF1 amino acid mutation is a missense mutation, including a missense mutation at amino acid position 257, such as RAF1:NM_002880.3:p.Ser257Leu:p.S257L; The RB1 amino acid mutation is a nonsense mutation and / or a splice site mutation and / or a frameshift mutation and / or a non-coding region mutation, including a nonsense mutation at amino acid position 787 and / or a frameshift mutation at amino acid position 73 and / or a nonsense mutation at amino acid position 48 and / or a nonsense mutation at amino acid position 251 and / or a frameshift mutation at amino acid position 450 and / or a splice site mutation and / or a non-coding region mutation, for example, RB1: NM_000321.2: p.Val4 50fs:p.V450Sfs*13, RB1:NM_000321.2:p.Glu48*:p.E48X, RB1:NM_000321.2:p.Arg73fs:p. R73Sfs*36, RB1:NM_000321.2:p.Arg787*:p.R787X, RB1:NM_000321.2:p.Arg251*:p.R251X; The RET amino acid mutation is a missense mutation, including a missense mutation at amino acid position 145, such as RET:NM_020975.6:p.Val145Ile:p.V145I; The SF3B1 amino acid mutation is a missense mutation, including a missense mutation at amino acid position 666, such as SF3B1:NM_012433.3:p.Lys666Asn:p.K666N; The SMAD4 amino acid mutation is a missense mutation and / or a nonsense mutation and / or a frameshift mutation, including a missense mutation at amino acid position 386 and / or a missense mutation at amino acid position 361 and / or a nonsense mutation at amino acid position 538 and / or a frameshift mutation at amino acid position 231, for example, SMAD4:NM_005359.6:p.Gly386Ser:p.G386S, SMAD4:NM_005359.6:p.Glu538*:p. E538X, SMAD4:NM_005359.6:p.Gly231fs:p.G231Afs*10, SMAD4:NM_005359.6:p.Arg361Ser:p.R 361S, SMAD4:NM_005359.6:p.Arg361Cys:p.R361C, SMAD4:NM_005359.6:p.Arg361His:p.R361H; The STK11 amino acid mutation is a nonsense mutation and / or a splice site mutation, including a nonsense mutation and / or a splice site mutation at amino acid position 308, such as STK11:NM_000455.5:p.Trp308*:p.W308X; The TERT amino acid mutation is a non-coding region mutation; The TP53 amino acid mutation is a nonsense mutation and / or a splice site mutation and / or a non-coding region mutation and / or a frameshift mutation and / or a missense mutation, including an amino acid mutation of TP53 being a frameshift region mutation of amino acids 27 to 330 and / or a nonsense mutation of amino acids 94 to 342 and / or a missense mutation of amino acids 110 to 337; The TSC1 amino acid mutation is a nonsense mutation, including a nonsense mutation at amino acid position 692 and / or a nonsense mutation at amino acid position 743 and / or a nonsense mutation at amino acid position 500, for example, TSC1:NM_000368.5:p.Arg692*:p.R692X, TSC1:NM_000368.5:p.Gln743*:p.Q743X, TSC1:NM_000368.5:p.Arg500*:p.R500X, TSC1:NM_000368.5:p.Arg692*:p.R692X; The TSC2 amino acid mutation is a nonsense mutation and / or a splice site mutation and / or a missense mutation, including a missense mutation at amino acid position 789 and / or a nonsense mutation at amino acid position 371 and / or a splice site mutation, for example, TSC2:NM_000548.5:p.Val789Ile:p.V789I, TSC2:NM_000548.5:p.Gln371*:p.Q371X; The TSHR amino acid mutation is a missense mutation, including a missense mutation at amino acid position 450 and / or a missense mutation at amino acid position 525, such as TSHR:NM_000369.3:p.Arg450His:p.R450H, TSHR:NM_000369.3:p.Phe525Ser:p.F525S; The UGT1A1 amino acid mutation is a missense mutation, including a missense mutation at amino acid position 229, such as UGT1A1:NM_000463.3:p.Pro229Gln:p.P229Q; The VEGFA amino acid mutation is a frameshift mutation, including an amino acid frameshift mutation at position 8, such as VEGFA:NM_001025366.3:p.Thr8fs:p.T8Rfs*78; The VHL amino acid mutation is a missense mutation, including a missense mutation at amino acid position 161, such as VHL:NM_000551.3:p.Arg161Gln:p.R161Q; The deleterious mutation is further preferably selected from any one of the following schemes: Scheme 1 CTNNB1:NM_001904.4:exon3:c.110C>G:p.Ser37Cys:p.S37C; and KRAS:NM_004985.5:exon2:c.38G>A:p.Gly13Asp:p.G13D; Scheme 2 CHEK2:NM_007194.4:exon13:c.1462-2A>G:-:-; and CHEK2:NM_007194.4:exon8:c.876delT:p.Phe292fs:p.F292Lfs*12; Scheme 3 MUTYH:NM_001128425.1:exon10:c.934-2A>G:-:-; Scheme 4 FOXL2:NM_023067.4:exon1:c.1045C>G:p.Arg349Gly:p.R349G; and PTEN:NM_000314.8:exon6:c.593T>A:p.Met198Lys:p.M198K; Scheme 5 ATM:NM_000051.3:exon51:c.7629+1G>A:-:-; and TP53:NM_000546.5:exon5:c.493C>T:p.Gln165*:p.Q165X; and UGT1A1:NM_000463.3:exon1:c.686C>A:p.Pro229Gln:p.P229Q; Scheme 6 CTNNB1:NM_001904.4:exon3:c.122C>T:p.Thr41Ile:p.T41I; and PIK3CA:NM_006218.4:exon10:c.1633G>A:p.Glu545Lys:p.E545K; and RB1:NM_000321.2:exon23:c.2359C>T:p.Arg787*:p.R787X; and TP53:NM_000546.5:exon7:c.782+1G>A:-:-; Scheme 7 ATM:NM_000051.3:exon5:c.496+1G>A:-:-; and TP53:NM_000546.5:exon4:c.216dupC:p.Val73fs:p.V73Rfs*76; Scheme 8 TP53:NM_000546.5:exon6:c.661G>T:p.Glu221*:p.E221X; Scheme 9 TP53:NM_000546.5:exon8:c.848G>C:p.Arg283Pro:p.R283P; Scheme 10 CTNNB1:NM_001904.4:exon3:c.133_135delTCT:p.Ser45del:p.S45del; Scheme 11 PTEN:NM_000314.8:exon5:c.403A>G:p.Ile135Val:p.I135V; Scheme 12 TP53:NM_000546.5:exon7:c.718A>C:p.Ser240Arg:p.S240R; Scheme 13 MUTYH:NM_001128425.1:exon10:c.934-2A>G:-:-; Scheme 14 TP53:NM_000546.5:exon7:c.730G>A:p.Gly244Ser:p.G244S; Scheme 15 TP53:NM_000546.5:exon6:c.638G>A:p.Arg213Gln:p.R213Q; Scheme 16 AR:NM_000044.6:exon6:c.2359C>T:p.Arg787*:p.R787X; and MUTYH:NM_001128425.1:exon10:c.934-2A>G:-:-; and PTEN:NM_000314.8:exon8:c.1026+1G>T:-:-; Scheme 17 UGT1A1:NM_000463.3:exon1:c.686C>A:p.Pro229Gln:p.P229Q; Scheme 18 APC:NM_000038.6:exon8:c.835-8A>G:-:-; and BRIP1:NM_032043.3:exon7:c.918+1G>A:-:-; and TP53:NM_000546.5:exon7:c.733G>A:p.Gly245Ser:p.G245S; and UGT1A1:NM_000463.3:exon1:c.686C>A:p.Pro229Gln:p.P229Q; Scheme 19 MUTYH:NM_001128425.1:exon10:c.934-2A>G:-:-; Scheme 20 NF1:NM_001042492.3:exon34:c.4498A>G:p.Ser1500Gly:p.S1500G; and TSC1:NM_000368.5:exon17:c.2074C>T:p.Arg692*:p.R692X; Scheme 21 CTNNB1:NM_001904.4:exon3:c.133T>C:p.Ser45Pro:p.S45P; and PTEN:NM_000314.8:exon8:c.955_958delACTT:p.Thr319fs:p.T319*; Scheme 22 ERBB2:NM_004448.3:exon8:c.929C>T:p.Ser310Phe:p.S310F; and PIK3CA:NM_006218.4:exon21:c.3140A>G:p.His1047Arg:p.H1047R; Scheme 23 TP53:NM_000546.5:exon5:c.413C>T:p.Ala138Val:p.A138V; Scheme 24 SMAD4:NM_005359.6:exon10:c.1156G>A:p.Gly386Ser:p.G386S; Scheme 25 CTNNB1:NM_001904.4:exon3:c.98C>T:p.Ser33Phe:p.S33F; and TP53:NM_000546.5:exon8:c.817C>T:p.Arg273Cys:p.R273C; Scheme 26 BRCA1:NM_007294.4:exon6:c.329dupA:p.Glu111fs:p.E111Gfs*3; and CDH1:NM_004360.5:exon9:c.1212delC:p.Asn405fs:p.N405Ifs*12; and TP53:NM_000546.5:exon4:c.216dupC:p.Val73fs:p.V73Rfs*76; Scheme 27 TP53:NM_000546.5:exon5:c.517G>T:p.Val173Leu:p.V173L; Scheme 28 APC:NM_000038.6:exon16:c.4348C>T:p.Arg1450*:p.R1450X; and APC:NM_000038.6:exon16:c.4393_4394delAG:p.Ser1465fs:p.S1465Wfs*3; and MLH1:NM_000249.3:exon10:c.793C>T:p.Arg265Cys:p.R265C; and TP53:NM_000546.5:exon8:c.797G>T:p.Gly266Val:p.G266V; Scheme 29 HNF1A:NM_000545.6:exon6:c.1129delC:p.Leu377fs:p.L377Sfs*7; Scheme 30 TP53:NM_000546.5:exon5:c.524G>T:p.Arg175Leu:p.R175L; Scheme 31 TP53:NM_000546.5:exon7:c.737T>A:p.Met246Lys:p.M246K; Scheme 32 FOXL2:NM_023067.4:exon1:c.1045C>G:p.Arg349Gly:p.R349G; and PTCH1:NM_000264.5:exon14:c.2178dupC:p.Cys727fs:p.C727Lfs*11; and TP53:NM_000546.5:exon6:c.644G>T:p.Ser215Ile:p.S215I; Scheme 33 ARID1A:NM_006015.6:exon1:c.175G>T:p.Glu59*:p.E59X; and CHEK2:NM_007194.4:exon14:c.1482G>C:p.Lys494Asn:p.K494N; Scheme 34 SMAD4:NM_005359.6:exon9:c.1082G>A:p.Arg361His:p.R361H; and TP53:NM_000546.5:exon8:c.811G>A:p.Glu271Lys:p.E271K; Scheme 35 CTNNB1:NM_001904.4:exon3:c.122C>T:p.Thr41Ile:p.T41I; and SMAD4:NM_005359.6:exon9:c.1081C>A:p.Arg361Ser:p.R361S; Scheme 36 TP53:NM_000546.5:exon8:c.818G>A:p.Arg273His:p.R273H; Scheme 37 TP53:NM_000546.5:exon7:c.701A>G:p.Tyr234Cys:p.Y234C; Scheme 38 PPP2R1A:NM_014225.6:exon5:c.544C>T:p.Arg182Trp:p.R182W; Scheme 39 PIK3CA:NM_006218.4:exon10:c.1633G>A:p.Glu545Lys:p.E545K; and TP53:NM_000546.5:exon5:c.527G>T:p.Cys176Phe:p.C176F; Scheme 40 CHEK2:NM_007194.4:exon12:c.1355G>A:p.Trp452*:p.W452X; and RAD51D:NM_002878.3:exon4:c.345+1G>A:-:-; and TP53:NM_000546.5:exon8:c.844C>T:p.Arg282Trp:p.R282W; Scheme 41 ATM:NM_000051.3:exon42:c.6100C>T:p.Arg2034*:p.R2034X; and TP53:NM_000546.5:exon5:c.413C>T:p.Ala138Val:p.A138V; and TP53:NM_000546.5:exon8:c.833C>T:p.Pro278Leu:p.P278L; and TSC2:NM_000548.5:exon21:c.2355+1G>A:-:-; Scheme 42 CTNNB1:NM_001904.4:exon3:c.110C>A:p.Ser37Tyr:p.S37Y; and FLT4:NM_182925.5:exon23:c.3121C>T:p.Arg1041Trp:p.R1041W; and TSC1:NM_000368.5:exon18:c.2227C>T:p.Gln743*:p.Q743X; Scheme 43 TERT:NM_198253.3:exon-:c.-124C>T:-:-; and TP53:NM_000546.5:exon7:c.730G>T:p.Gly244Cys:p.G244C; Scheme 44 CTNNB1:NM_001904.4:exon3:c.110C>G:p.Ser37Cys:p.S37C; and SMAD4:NM_005359.6:exon9:c.1082G>A:p.Arg361His:p.R361H; and TP53:NM_000546.5:exon8:c.853G>A:p.Glu285Lys:p.E285K; Scheme 45 APC:NM_000038.6:exon16:c.3688C>T:p.Gln1230*:p.Q1230X; and TERT:NM_198253.3:exon-:c.-124C>T:-:-; Scheme 46 APC:NM_000038.6:exon12:c.1548+1G>A:-:-; and AR:NM_000044.6:exon7:c.2599G>A:p.Val867Met:p.V867M; and RAD51C:NM_058216.3:exon5:c.709C>T:p.Arg237*:p.R237X; and RB1:NM_000321.2:exon13:c.1332+1G>A:-:-; and RB1:NM_000321.2:exon19:c.1960+1G>T:-:-; and TP53:NM_000546.5:exon5:c.430C>T:p.Gln144*:p.Q144X; Scheme 47 TP53:NM_000546.5:exon5:c.481G>A:p.Ala161Thr:p.A161T; Scheme 48 TP53:NM_000546.5:exon8:c.814G>A:p.Val272Met:p.V272M; Scheme 49 TP53:NM_000546.5:exon4:c.159G>A:p.Trp53*:p.W53X; Scheme 50 CDKN2A:NM_000077.4:exon2:c.247C>T:p.His83Tyr:p.H83Y; Scheme 51 TP53:NM_000546.5:exon8:c.814G>T:p.Val272Leu:p.V272L; Scheme 52 ATM:NM_000051.3:exon49:c.7307G>A:p.Arg2436Lys:p.R2436K; Scheme 53 PIK3CA:NM_006218.4:exon5:c.1030G>A:p.Val344Met:p.V344M; and TP53:NM_000546.5:exon7:c.742C>T:p.Arg248Trp:p.R248W; Scheme 54 CTNNB1:NM_001904.4:exon3:c.98C>G:p.Ser33Cys:p.S33C; and FGFR1:NM_023110.3:exon4:c.448+1G>A:-:-; and MSH6:NM_000179.2:exon4:c.2927G>A:p.Arg976His:p.R976H; Scheme 55 KIT:NM_000222.2:exon5:c.910A>G:p.Thr304Ala:p.T304A; and MTHFR:NM_005957.5:exon5:c.680C>T:p.Thr227Met:p.T227M; Scheme 56 MUTYH:NM_001128425.1:exon13:c.1187G>A:p.Gly396Asp:p.G396D; Scheme 57 TP53:NM_000546.5:exon7:c.761T>C:p.Ile254Thr:p.I254T; Scheme 58 CTNNB1:NM_001904.4:exon3:c.101G>A:p.Gly34Glu:p.G34E; and NF1:NM_001042492.3:exon25:c.3315-1G>T:-:-; and NF1:NM_001042492.3:exon38:c.5609G>A:p.Arg1870Gln:p.R1870Q; Scheme 59 CTNNB1:NM_001904.4:exon3:c.110C>G:p.Ser37Cys:p.S37C; and TP53:NM_000546.5:exon8:c.853G>A:p.Glu285Lys:p.E285K; and TP53:NM_000546.5:exon5:c.518T>C:p.Val173Ala:p.V173A; Scheme 60 TP53:NM_000546.5:exon6:c.626_627delGA:p.Arg209fs:p.R209Kfs*6; Scheme 61 TP53:NM_000546.5:exon4:c.298C>T:p.Gln100*:p.Q100X; Scheme 62 ATM:NM_000051.3:exon49:c.7141_7151delAATGGAAAAAT:p.Asn2381fs:p.N2381Efs*18; and BRIP1:NM_032043.3:exon8:c.1078C>T:p.Gln360*:p.Q360X; Scheme 63 PIK3CA:NM_006218.4:exon2:c.323G>A:p.Arg108His:p.R108H; and TP53:NM_000546.5:exon5:c.541C>T:p.Arg181Cys:p.R181C; Scheme 64 NF1:NM_001042492.3:exon12:c.1381C>T:p.Arg461*:p.R461X; and RAF1:NM_002880.3:exon7:c.770C>T:p.Ser257Leu:p.S257L; and RB1:NM_000321.2:exon20:c.2107-1G>C:-:-; and TP53:NM_000546.5:exon5:c.524G>A:p.Arg175His:p.R175H; Scheme 65 FOXL2:NM_023067.4:exon1:c.1045C>G:p.Arg349Gly:p.R349G; Scheme 66 BRCA2:NM_000059.3:exon7:c.631+1G>A:-:-; and NF1:NM_001042492.3:exon9:c.1062+1G>A:-:-; Scheme 67 ERBB4:NM_005235.3:exon2:c.119_120delCT:p.Ser40fs:p.S40*; and TP53:NM_000546.5:exon5:c.473G>T:p.Arg158Leu:p.R158L; and VHL:NM_000551.3:exon3:c.482G>A:p.Arg161Gln:p.R161Q; Scheme 68 PIK3CA:NM_006218.4:exon10:c.1633G>A:p.Glu545Lys:p.E545K; Scheme 69 TP53:NM_000546.5:exon6:c.659A>G:p.Tyr220Cys:p.Y220C; Scheme 70 TP53:NM_000546.5:exon6:c.577C>T:p.His193Tyr:p.H193Y; Scheme 71 ATM:NM_000051.3:exon5:c.468G>A:p.Trp156*:p.W156X; Scheme 72 BRCA2:NM_000059.3:exon15:c.7522G>A:p.Gly2508Ser:p.G2508S; and TP53:NM_000546.5:exon5:c.538G>A:p.Glu180Lys:p.E180K; Scheme 73 MUTYH:NM_001128425.1:exon10:c.934-2A>G:-:-; and PALB2:NM_024675.4:exon4:c.1213C>G:p.Pro405Ala:p.P405A; and TP53:NM_000546.5:exon6:c.646G>A:p.Val216Met:p.V216M; Scheme 74 TP53:NM_000546.5:exon5:c.527G>A:p.Cys176Tyr:p.C176Y; Scheme 75 UGT1A1:NM_000463.3:exon1:c.686C>A:p.Pro229Gln:p.P229Q; Scheme 76 CDKN2A:NM_000077.4:exon1:c.32dupC:p.Ser12fs:p.S12Ffs*3; and TP53:NM_000546.5:exon9:c.991C>T:p.Gln331*:p.Q331X; Scheme 77 TP53:NM_000546.5:exon7:c.783-1G>T:-:-; and VEGFA:NM_001025366.3:exon1:c.19_22dupGACA:p.Thr8fs:p.T8Rfs*78; Scheme 78 TP53:NM_000546.5:exon5:c.503A>G:p.His168Arg:p.H168R; Scheme 79 CTNNB1:NM_001904.4:exon3:c.101G>T:p.Gly34Val:p.G34V; and TP53:NM_000546.5:exon8:c.817C>T:p.Arg273Cys:p.R273C; and TSC1:NM_000368.5:exon15:c.1498C>T:p.Arg500*:p.R500X; Scheme 80 TP53:NM_000546.5:exon8:c.841G>C:p.Asp281His:p.D281H; and UGT1A1:NM_000463.3:exon1:c.686C>A:p.Pro229Gln:p.P229Q; Scheme 81 ATM:NM_000051.3:exon46:c.6807G>A:p.Gln2269Gln:p.Q2269Q; and CHEK2:NM_007194.4:exon3:c.409C>T:p.Arg137*:p.R137X; and CTNNB1:NM_001904.4:exon3:c.98C>G:p.Ser33Cys:p.S33C; and PIK3R1:NM_181523.3:exon11:c.1425+1G>A:-:-; and TP53:NM_000546.5:exon5:c.532delC:p.His178fs:p.H178Tfs*69; and TSC1:NM_000368.5:exon17:c.2074C>T:p.Arg692*:p.R692X; Scheme 82 TP53:NM_000546.5:exon6:c.644G>T:p.Ser215Ile:p.S215I; Scheme 83 UGT1A1:NM_000463.3:exon1:c.686C>A:p.Pro229Gln:p.P229Q; Scheme 84 ARID1A:NM_006015.6:exon1:c.437delC:p.Pro146fs:p.P146Qfs*86; and BRCA2:NM_000059.3:exon5:c.475+3A>G:-:-; and BTK:NM_000061.2:exon15:c.1455C>A:p.Tyr485*:p.Y485X; and TP53:NM_000546.5:exon9:c.994-1G>A:-:-; Scheme 85 PDGFRA:NM_006206.6:exon22:c.3098A>T:p.Asp1033Val:p.D1033V; and TP53:NM_000546.5:exon5:c.527G>T:p.Cys176Phe:p.C176F; Scheme 86 TP53:NM_000546.5:exon7:c.743G>T:p.Arg248Leu:p.R248L; Scheme 87 BRCA1:NM_007294.4:exon10:c.811G>A:p.Val271Met:p.V271M; Scheme 88 CTNNB1:NM_001904.4:exon3:c.94G>A:p.Asp32Asn:p.D32N; Scheme 89 TP53:NM_000546.5:exon7:c.743G>A:p.Arg248Gln:p.R248Q; Scheme 90 CTNNB1:NM_001904.4:exon3:c.101G>A:p.Gly34Glu:p.G34E; and PIK3CA:NM_006218.4:exon10:c.1633G>A:p.Glu545Lys:p.E545K; Scheme 91 TP53:NM_000546.5:exon10:c.1024C>T:p.Arg342*:p.R342X; Scheme 92 TP53:NM_000546.5:exon4:c.374C>T:p.Thr125Met:p.T125M; and TP53:NM_000546.5:exon8:c.853G>A:p.Glu285Lys:p.E285K; and TP53:NM_000546.5:exon8:c.839G>C:p.Arg280Thr:p.R280T; Scheme 93 POLE:NM_006231.4:exon5:c.424-1G>A:-:-; and SMAD4:NM_005359.6:exon9:c.1082G>A:p.Arg361His:p.R361H; and TP53:NM_000546.5:exon6:c.641A>G:p.His214Arg:p.H214R; Scheme 94 TP53:NM_000546.5:exon5:c.421T>C:p.Cys141Arg:p.C141R; Scheme 95 CTNNB1:NM_001904.4:exon3:c.94G>C:p.Asp32His:p.D32H; and PIK3CA:NM_006218.4:exon21:c.3140A>G:p.His1047Arg:p.H1047R; Scheme 96 TSC2:NM_000548.5:exon22:c.2365G>A:p.Val789Ile:p.V789I; Scheme 97 BRIP1:NM_032043.3:exon19:c.2789C>A:p.Ser930*:p.S930X; and CTNNB1:NM_001904.4:exon3:c.110C>T:p.Ser37Phe:p.S37F; and FGFR2:NM_000141.4:exon8:c.1075G>A:p.Val359Ile:p.V359I; and KDM6A:NM_001291415.1:exon18:c.2858+1G>A:-:-; and NF1:NM_001042492.3:exon5:c.484C>T:p.Gln162*:p.Q162X; and TSC2:NM_000548.5:exon11:c.1111C>T:p.Gln371*:p.Q371X; Scheme 98 RB1:NM_000321.2:exon22:c.2325+1G>A:-:-; and SMAD4:NM_005359.6:exon12:c.1612G>T:p.Glu538*:p.E538X; Scheme 99 ATM:NM_000051.3:exon50:c.7355T>C:p.Leu2452Pro:p.L2452P; Scheme 100 TP53:NM_000546.5:exon5:c.422G>A:p.Cys141Tyr:p.C141Y; Scheme 101 CTNNB1:NM_001904.4:exon3:c.94G>T:p.Asp32Tyr:p.D32Y; and PIK3CA:NM_006218.4:exon21:c.3140A>T:p.His1047Leu:p.H1047L; Scheme 102 TP53:NM_000546.5:exon8:c.920-2A>G:-:-; Scheme 103 BRIP1:NM_032043.3:exon7:c.632delC:p.Pro211fs:p.P211Lfs*63; and CTNNB1:NM_001904.4:exon3:c.98C>G:p.Ser33Cys:p.S33C; and CTNNB1:NM_001904.4:exon3:c.110C>G:p.Ser37Cys:p.S37C; Scheme 104 BRCA2:NM_000059.3:exon15:c.7522G>A:p.Gly2508Ser:p.G2508S; and PIK3CA:NM_006218.4:exon21:c.3129G>T:p.Met1043Ile:p.M1043I; and TP53:NM_000546.5:exon7:c.743G>A:p.Arg248Gln:p.R248Q; Scheme 105 MUTYH:NM_001128425.1:exon10:c.934-2A>G:-:-; and TP53:NM_000546.5:exon4:c.376-1G>A:-:-; Scheme 106 CTNNB1:NM_001904.4:exon3:c.110C>T:p.Ser37Phe:p.S37F; Scheme 107 TP53:NM_000546.5:exon5:c.398T>C:p.Met133Thr:p.M133T Scheme 108 ETV6:NM_001987.5:exon7:c.1195C>T:p.Arg399Cys:p.R399C; Scheme 109 TP53:NM_000546.5:exon5:c.469G>T:p.Val157Phe:p.V157F; Scheme 110 RET:NM_020975.6:exon3:c.433G>A:p.Val145Ile:p.V145I; Scheme 111 CTNNB1:NM_001904.4:exon3:c.110C>T:p.Ser37Phe:p.S37F; and TP53:NM_000546.5:exon6:c.638G>A:p.Arg213Gln:p.R213Q; and TP53:NM_000546.5:exon5:c.527G>T:p.Cys176Phe:p.C176F; Scheme 112 TP53:NM_000546.5:exon4:c.102delC:p.Leu35fs:p.L35Cfs*9; Scheme 113 TP53:NM_000546.5:exon8:c.832C>A:p.Pro278Thr:p.P278T; Scheme 114 TP53:NM_000546.5:exon9:c.988delC:p.Leu330fs:p.L330Ffs*15; Scheme 115 PIK3CA:NM_006218.4:exon10:c.1633G>A:p.Glu545Lys:p.E545K; and PTEN:NM_000314.8:exon6:c.511C>G:p.Gln171Glu:p.Q171E; and TP53:NM_000546.5:exon8:c.844C>G:p.Arg282Gly:p.R282G; Scheme 116 APC:NM_000038.6:exon16:c.2299C>T:p.Gln767*:p.Q767X; and TP53:NM_000546.5:exon6:c.659A>G:p.Tyr220Cys:p.Y220C; Scheme 117 PTEN:NM_000314.8:exon9:c.1211G>C:p.Ter404Serext*:p.X404S; and TP53:NM_000546.5:exon3:c.80delC:p.Pro27fs:p.P27Lfs*17; Scheme 118 ATM:NM_000051.3:exon55:c.8071C>T:p.Arg2691Cys:p.R2691C; and RB1:NM_000321.2:exon2:c.219_220delAG:p.Arg73fs:p.R73Sfs*36; and TP53:NM_000546.5:exon8:c.818G>C:p.Arg273Pro:p.R273P; Scheme 119 TP53:NM_000546.5:exon7:c.725G>T:p.Cys242Phe:p.C242F; Scheme 120 BRAF:NM_004333.6:exon11:c.1397G>A:p.Gly466Glu:p.G466E; Scheme 121 CDKN2A:NM_000077.4:exon2:c.387C>A:p.Tyr129*:p.Y129X; Scheme 122 TP53:NM_000546.5:exon7:c.734G>A:p.Gly245Asp:p.G245D; Scheme 123 PIK3CA:NM_006218.4:exon10:c.1637A>G:p.Gln546Arg:p.Q546R; Scheme 124 CTNNB1:NM_001904.4:exon3:c.98C>G:p.Ser33Cys:p.S33C; and CTNNB1:NM_001904.4:exon3:c.110C>A:p.Ser37Tyr:p.S37Y; TP53:NM_000546.5:exon5:c.455C>T:p.Pro152Leu:p.P152L; Scheme 125 TP53:NM_000546.5:exon7:c.745A>T:p.Arg249Trp:p.R249W; and VEGFA:NM_001025366.3:exon1:c.19_22dupGACA:p.Thr8fs:p.T8Rfs*78; Scheme 126 TP53:NM_000546.5:exon4:c.281C>A:p.Ser94*:p.S94X; Scheme 127 TP53:NM_000546.5:exon7:c.776A>T:p.Asp259Val:p.D259V; Scheme 128 FOXL2:NM_023067.4:exon1:c.1045C>G:p.Arg349Gly:p.R349G; Scheme 129 AR:NM_000044.6:exon1:c.902A>G:p.Lys301Arg:p.K301R; and TP53:NM_000546.5:exon5:c.464C>A:p.Thr155Asn:p.T155N; Scheme 130 TP53:NM_000546.5:exon5:c.389T>A:p.Leu130His:p.L130H; Scheme 131 TP53:NM_000546.5:exon5:c.404G>T:p.Cys135Phe:p.C135F; Scheme 132 BRIP1:NM_032043.3:exon16:c.2324A>G:p.Asn775Ser:p.N775S; Scheme 133 TP53:NM_000546.5:exon5:c.451C>T:p.Pro151Ser:p.P151S; Scheme 134 NTRK1:NM_002529.3:exon15:c.1945C>T:p.Arg649Trp:p.R649W; Scheme 135 NFE2L2:NM_006164.5:exon2:c.85G>C:p.Asp29His:p.D29H; and SMAD4:NM_005359.6:exon9:c.1081C>T:p.Arg361Cys:p.R361C; and STK11:NM_000455.5:exon8:c.923G>A:p.Trp308*:p.W308X; Scheme 136 TP53:NM_000546.5:exon8:c.823T>C:p.Cys275Arg:p.C275R; Scheme 137 FOXL2:NM_023067.4:exon1:c.1045C>G:p.Arg349Gly:p.R349G; and TP53:NM_000546.5:exon6:c.615T>A:p.Tyr205*:p.Y205X; Scheme 138 ALK:NM_004304.5:exon3:c.872G>A:p.Arg291His:p.R291H; and APC:NM_000038.6:exon16:c.2626C>T:p.Arg876*:p.R876X; Scheme 139 BRCA1:NM_007294.4:exon10:c.1465G>T:p.Glu489*:p.E489X; and FOXL2:NM_023067.4:exon1:c.1045C>G:p.Arg349Gly:p.R349G; and NBN:NM_002485.4:exon1:c.3G>A:p.Met1:p.M1; and NTRK1:NM_002529.3:exon14:c.1768G>A:p.Glu590Lys:p.E590K; and TP53:NM_000546.5:exon9:c.949C>T:p.Gln317*:p.Q317X; Scheme 140 MPL:NM_005373.3:exon3:c.235_236delCT:p.Leu79fs:p.L79Efs*84; and TP53:NM_000546.5:exon6:c.646G>T:p.Val216Leu:p.V216L; Scheme 141 TP53:NM_000546.5:exon5:c.535C>G:p.His179Asp:p.H179D; and UGT1A1:NM_000463.3:exon1:c.686C>A:p.Pro229Gln:p.P229Q Scheme 142 TSHR:NM_000369.3:exon10:c.1349G>A:p.Arg450His:p.R450H; Scheme 143 TP53:NM_000546.5:exon7:c.742C>T:p.Arg248Trp:p.R248W; Scheme 144 TP53:NM_000546.5:exon3:c.97-1G>A:-:-; Scheme 145 TP53:NM_000546.5:exon5:c.455C>G:p.Pro152Arg:p.P152R; Scheme 146 TP53:NM_000546.5:exon9:c.993+1G>T:-:-; Scheme 147 TP53:NM_000546.5:exon7:c.707A>G:p.Tyr236Cys:p.Y236C; Scheme 148 CTNNB1:NM_001904.4:exon3:c.100G>A:p.Gly34Arg:p.G34R; and TP53:NM_000546.5:exon4:c.159G>A:p.Trp53*:p.W53X; Scheme 140 TP53:NM_000546.5:exon8:c.818G>A:p.Arg273His:p.R273H; Scheme 150 PTEN:NM_000314.8:exon3:c.209+5G>A:-:-; Scheme 151 ATM:NM_000051.3:exon49:c.7141_7151delAATGGAAAAAT:p.Asn2381fs:p.N2381Efs*18; Scheme 152 STK11:NM_000455.5:exon1:c.291-2A>G:-:-; and TP53:NM_000546.5:exon7:c.743G>A:p.Arg248Gln:p.R248Q; Scheme 153 TP53:NM_000546.5:exon8:c.830G>T:p.Cys277Phe:p.C277F; Scheme 154 PDGFRA:NM_006206.6:exon22:c.3098A>T:p.Asp1033Val:p.D1033V; Scheme 155 TP53:NM_000546.5:exon8:c.841G>C:p.Asp281His:p.D281H; Scheme 156 TP53:NM_000546.5:exon5:c.469G>T:p.Val157Phe:p.V157F; Scheme 157 NTRK1:NM_002529.3:exon17:c.2303C>T:p.Pro768Leu:p.P768L; and TP53:NM_000546.5:exon5:c.388C>T:p.Leu130Phe:p.L130F; Scheme 158 TP53:NM_000546.5:exon5:c.403T>C:p.Cys135Arg:p.C135R; Scheme 159 NF1:NM_001042492.3:exon33:c.4339C>T:p.Gln1447*:p.Q1447X; and TP53:NM_000546.5:exon9:c.927delC:p.Asn310fs:p.N310Tfs*35; Scheme 160 SF3B1:NM_012433.3:exon14:c.1998G>C:p.Lys666Asn:p.K666N; and TP53:NM_000546.5:exon4:c.375+1G>T:-:-; Scheme 161 FANCA:NM_000135.4:exon39:c.3906G>A:p.Trp1302*:p.W1302X; Scheme 162 TP53:NM_000546.5:exon6:c.637C>T:p.Arg213*:p.R213X; Scheme 163 TP53:NM_000546.5:exon4:c.154C>T:p.Gln52*:p.Q52X; Scheme 164 IDH2:NM_002168.3:exon4:c.419G>A:p.Arg140Gln:p.R140Q; and PIK3CA:NM_006218.4:exon10:c.1633G>A:p.Glu545Lys:p.E545K; and TP53:NM_000546.5:exon10:c.1010G>A:p.Arg337His:p.R337H; Scheme 165 TP53:NM_000546.5:exon4:c.310C>T:p.Gln104*:p.Q104X; Scheme 166 BRCA2:NM_000059.3:exon15:c.7522G>A:p.Gly2508Ser:p.G2508S; and TP53:NM_000546.5:exon10:c.1024C>T:p.Arg342*:p.R342X; Scheme 167 TP53:NM_000546.5:exon6:c.673-1G>T:-:-; Scheme 168 TP53:NM_000546.5:exon8:c.836G>A:p.Gly279Glu:p.G279E; Scheme 169 RB1:NM_000321.2:exon2:c.142G>T:p.Glu48*:p.E48X; and TP53:NM_000546.5:exon8:c.919+2T>A:-:-; Scheme 170 PIK3CA:NM_006218.4:exon10:c.1624G>A:p.Glu542Lys:p.E542K; and RB1:NM_000321.2:exon8:c.751C>T:p.Arg251*:p.R251X; and TP53:NM_000546.5:exon4:c.337T>G:p.Phe113Val:p.F113V; Scheme 171 MUTYH:NM_001128425.1:exon10:c.934-2A>G:-:-; and NF1:NM_001042492.3:exon23:c.3113G>C:p.Arg1038Thr:p.R1038T; Scheme 172 NF1:NM_001042492.3:exon33:c.4339C>G:p.Gln1447Glu:p.Q1447E; and PIK3CA:NM_006218.4:exon10:c.1633G>A:p.Glu545Lys:p.E545K; and TP53:NM_000546.5:exon8:c.856G>A:p.Glu286Lys:p.E286K; Scheme 173 PIK3CA:NM_006218.4:exon8:c.1357G>C:p.Glu453Gln:p.E453Q; and PIK3CA:NM_006218.4:exon19:c.2702G>T:p.Cys901Phe:p.C901F; and TP53:NM_000546.5:exon7:c.722C>T:p.Ser241Phe:p.S241F; Scheme 174 APC:NM_000038.6:exon5:c.481C>T:p.Gln161*:p.Q161X; and TP53:NM_000546.5:exon8:c.817C>T:p.Arg273Cys:p.R273C; Scheme 175 TP53:NM_000546.5:exon5:c.524G>A:p.Arg175His:p.R175H; Scheme 176 PIK3CA:NM_006218.4:exon10:c.1633G>A:p.Glu545Lys:p.E545K; and TP53:NM_000546.5:exon7:c.742C>G:p.Arg248Gly:p.R248G; Scheme 177 CHEK2:NM_007194.4:exon11:c.1260-1G>A:-:-; and PTEN:NM_000314.8:exon2:c.107G>A:p.Gly36Glu:p.G36E; and TP53:NM_000546.5:exon5:c.524G>A:p.Arg175His:p.R175H; Scheme 178 UGT1A1:NM_000463.3:exon1:c.686C>A:p.Pro229Gln:p.P229Q; Scheme 179 TP53:NM_000546.5:exon5:c.523C>G:p.Arg175Gly:p.R175G; Scheme 180 FOXL2:NM_023067.4:exon1:c.1045C>G:p.Arg349Gly:p.R349G; and PTEN:NM_000314.8:exon5:c.464A>G:p.Tyr155Cys:p.Y155C; and PTEN:NM_000314.8:exon6:c.518G>C:p.Arg173Pro:p.R173P; and TP53:NM_000546.5:exon10:c.1024C>T:p.Arg342*:p.R342X; and TSHR:NM_000369.3:exon10:c.1574T>C:p.Phe525Ser:p.F525S; Scheme 181 RB1:NM_000321.2:exon14:c.1346dupG:p.Val450fs:p.V450Sfs*13; Scheme 182 TP53:NM_000546.5:exon5:c.404G>A:p.Cys135Tyr:p.C135Y; Scheme 183 NF2:NM_000268.3:exon13:c.1396C>T:p.Arg466*:p.R466X; Scheme 184 APC:NM_000038.6:exon16:c.2926delA:p.Arg976fs:p.R976Efs*4; and FOXL2:NM_023067.4:exon1:c.1045C>G:p.Arg349Gly:p.R349G; and PALB2:NM_024675.4:exon5:c.2038G>T:p.Gly680*:p.G680X; and TP53:NM_000546.5:exon7:c.734G>T:p.Gly245Val:p.G245V; and TSHR:NM_000369.3:exon10:c.1574T>C:p.Phe525Ser:p.F525S; Scheme 185 TP53:NM_000546.5:exon7:c.746G>A:p.Arg249Lys:p.R249K; Scheme 186 PIK3CA:NM_006218.4:exon10:c.1624G>C:p.Glu542Gln:p.E542Q; and TP53:NM_000546.5:exon6:c.638G>C:p.Arg213Pro:p.R213P; Scheme 187 PDGFRA:NM_006206.6:exon11:c.1631T>C:p.Val544Ala:p.V544A; Scheme 188 GATA3:NM_001002295.2:exon3:c.431delG:p.Gly144fs:p.G144Afs*51; and PIK3CA:NM_006218.4:exon10:c.1633G>A:p.Glu545Lys:p.E545K; Scheme 189 TP53:NM_000546.5:exon6:c.578A>G:p.His193Arg:p.H193R; Scheme 190 RB1:NM_000321.2:exon21:c.2211+5G>A:-:-; and TP53:NM_000546.5:exon8:c.817C>T:p.Arg273Cys:p.R273C; Scheme 191 TP53:NM_000546.5:exon7:c.718A>G:p.Ser240Gly:p.S240G; Scheme 192 TP53:NM_000546.5:exon10:c.1009C>T:p.Arg337Cys:p.R337C; Scheme 193 TP53:NM_000546.5:exon7:c.783-2A>C:-:-; Scheme 194 BRCA2:NM_000059.3:exon21:c.8702G>A:p.Gly2901Asp:p.G2901D; and TP53:NM_000546.5:exon5:c.499C>T:p.Gln167*:p.Q167X; Scheme 195 ALK:NM_004304.5:exon9:c.1648C>T:p.Leu550Phe:p.L550F; Scheme 196 TP53:NM_000546.5:exon3:c.97-2delA:-:-; Scheme 197 ATM:NM_000051.3:exon57:c.8373C>A:p.Tyr2791*:p.Y2791X; and IDH1:NM_005896.3:exon4:c.394C>T:p.Arg132Cys:p.R132C; and PDGFRA:NM_006206.6:exon22:c.2942G>A:p.Arg981His:p.R981H; Scheme 198 BRCA1:NM_007294.4:exon10:c.2952delT:p.Ile986fs:p.I986Sfs*14; and CHEK2:NM_007194.4:exon4:c.538C>T:p.Arg180Cys:p.R180C; and PALB2:NM_024675.4:exon4:c.1546delA:p.Arg516fs:p.R516Efs*45; and PPP2R1A:NM_014225.6:exon6:c.656C>T:p.Ser219Leu:p.S219L; and SMAD4:NM_005359.6:exon6:c.692delG:p.Gly231fs:p.G231Afs*10; and VEGFA:NM_001025366.3:exon1:c.19_22dupGACA:p.Thr8fs:p.T8Rfs*78; Scheme 199 APC:NM_000038.6:exon16:c.7932_7935delTTAT:p.Tyr2645fs:p.Y2645Kfs*14; Scheme 200 TP53:NM_000546.5:exon4:c.329G>T:p.Arg110Leu:p.R110L; Scheme 201 POLE:NM_006231.4:exon13:c.1270C>G:p.Leu424Val:p.L424V. In some preferred embodiments, a compound having a structure of Formula I or a pharmaceutically acceptable salt thereof is provided for use in preparing a drug for treating a disease associated with EGFR mutation combined with TP53 deleterious mutation. The TP53 deleterious mutation is an exon mutation, including exon mutations 3 to 10, preferably nonsense mutations and / or splice site mutations and / or non-coding region mutations and / or frameshift mutations and / or missense mutations in exons 3 to 10; For example, TP53:NM_000546.5:exon10:c.1009C>T, TP53:NM_000546.5:exon10:c.1010G>A, TP53:NM_000546.5:exon10:c.1024C>T, TP53:NM_000546.5:exon3:c.80delC, TP53:NM_000546.5:exon3:c.97-1G>A, TP53:NM_000546.5:exon3:c.97-2delA, TP53:NM_000546.5:exon4:c.102delC, TP53:NM_000546.5:exon4:c.154C>T, TP53:NM_000546.5:exon4:c.159G>A, TP53:NM_000546.5:exon4:c.216dupC, TP53:NM_000546.5:exon4:c.281C>A, TP53:NM_000546.5:exon4:c.298C>T, TP53:NM_000546.5:exon4:c.310C>T, TP53:NM_000546.5:exon4:c.329G>T, TP53:NM_000546.5:exon4:c.337T>G, TP53:NM_000546.5:exon4:c.374C>T, TP53:NM_000546.5:exon4:c.375+1G>T, TP53:NM_000546.5:exon4:c.376-1G>A, TP53:NM_000546.5:exon5:c.388C>T, TP53:NM_000546.5:exon5:c.389T>A:, TP53:NM_000546.5:exon5:c.398T>C, TP53:NM_000546.5:exon5:c.403T>C, TP53:NM_000546.5:exon5:c.404G>A, TP53:NM_000546.5:exon5:c.404G>T, TP53:NM_000546.5:exon5:c.413C>T, TP53:NM_000546.5:exon5:c.421T>C, TP53:NM_000546.5:exon5:c.422G>A, TP53:NM_000546.5:exon5:c.430C>T, TP53:NM_000546.5:exon5:c.451C>T, TP53:NM_000546.5:exon5:c.455C>G, TP53:NM_000546.5:exon5:c.455C>T:、TP53:NM_000546.5:exon5:c.464C>A、TP53:NM_000546.5:exon5:c.469G>T、TP53:NM_000546.5:exon5:c.473G>T、TP53:NM_000546.5:exon5:c.481G>A、TP53:NM_000546.5:exon5:c.493C>T、TP53:NM_000546.5:exon5:c.499C>T、TP53:NM_000546.5:exon5:c.503A>G、TP53:NM_000546.5:exon5:c.517G>T、TP53:NM_000546.5:exon5:c.518T>C、TP53:NM_000546.5:exon5:c.523C>G、TP53:NM_000546.5:exon5:c.524G>A、TP53:NM_000546.5:exon5:c.524G>T、TP53:NM_000546.5:exon5:c.527G>A、TP53:NM_000546.5:exon5:c.527G>T、TP53:NM_000546.5:exon5:c.532delC、TP53:NM_000546.5:exon5:c.535C>G:、TP53:NM_000546.5:exon5:c.538G>A、TP53:NM_000546.5:exon5:c.541C>T、TP53:NM_000546.5:exon6:c.577C>T、TP53:NM_000546.5:exon6:c.578A>G、TP53:NM_000546.5:exon6:c.615T>A、TP53:NM_000546.5:exon6:c.626_627delGA、TP53:NM_000546.5:exon6:c.637C>T、TP53:NM_000546.5:exon6:c.638G>A、TP53:NM_000546.5:exon6:c.638G>C、TP53:NM_000546.5:exon6:c.641A>G、TP53:NM_000546.5:exon6:c.644G>T、TP53:NM_000546.5:exon6:c.646G>A、TP53:NM_000546.5:exon6:c.646G>T、TP53:NM_000546.5:exon6:c.659A>G、TP53:NM_000546.5:exon6:c.661G>T、TP53:NM_000546.5:exon6:c.673-1G>T、TP53:NM_000546.5:exon7:c.701A>G、TP53:NM_000546.5:exon7:c.707A>G、TP53:NM_000546.5:exon7:c.718A>C、TP53:NM_000546.5:exon7:c.718A>G、TP53:NM_000546.5:exon7:c.722C>T、TP53:NM_000546.5:exon7:c.725G>T、TP53:NM_000546.5:exon7:c.730G>A、TP53:NM_000546.5:exon7:c.730G>T、TP53:NM_000546.5:exon7:c.733G>A、TP53:NM_000546.5:exon7:c.734G>A、TP53:NM_000546.5:exon7:c.734G>T、TP53:NM_000546.5:exon7:c.737T>A:、TP53:NM_000546.5:exon7:c.742C>G、TP53:NM_000546.5:exon7:c.742C>T、TP53:NM_000546.5:exon7:c.743G>A、TP53:NM_000546.5:exon7:c.743G>T、TP53:NM_000546.5:exon7:c.745A>T、TP53:NM_000546.5:exon7:c.746G>A、TP53:NM_000546.5:exon7:c.761T>C、TP53:NM_000546.5:exon7:c.776A>T、TP53:NM_000546.5:exon7:c.782+1G>A、TP53:NM_000546.5:exon7:c.783-1G>T、TP53:NM_000546.5:exon7:c.783-2A>C、TP53:NM_000546.5:exon8:c.797G>T、TP53:NM_000546.5:exon8:c.811G>A、TP53:NM_000546.5:exon8:c.814G>A、TP53:NM_000546.5:exon8:c.814G>T、TP53:NM_000546.5:exon8:c.817C>T、TP53:NM_000546.5:exon8:c.818G>A:, TP53:NM_000546.5:exon8:c.818G>C:, TP53:NM_000546.5:exon8:c.823T>C, TP53:NM_00054 6.5:exon8:c.830G>T, TP53:NM_000546.5:exon8:c.832C>A, TP53:NM_000546.5:exon8:c.833C>T, TP53 :NM_000546.5:exon8:c.836G>A, TP53:NM_000546.5:exon8:c.839G>C, TP53:NM_000546.5:exon8:c.8 41G>C, TP53:NM_000546.5:exon8:c.844C>G, TP53:NM_000546.5:exon8:c.844C>T, TP53:NM_000546.5: exon8:c.848G>C, TP53:NM_000546.5:exon8:c.853G>A, TP53:NM_000546.5:exon8:c.856G>A, TP53:NM _000546.5:exon8:c.919+2T>A, TP53:NM_000546.5:exon8:c.920-2A>G, TP53:NM_000546.5:exon9:c.9 27delC, TP53:NM_000546.5:exon9:c.949C>T, TP53:NM_000546.5:exon9:c.988delC, TP53:NM_000546 .5:exon9:c.991C>T, TP53:NM_000546.5:exon9:c.993+1G>T, TP53:NM_000546.5:exon9:c.994-1G>A;. and / or, The amino acid mutation of TP53 is a nonsense mutation and / or a splice site mutation and / or a non-coding region mutation and / or a frameshift mutation and / or a missense mutation, including an amino acid mutation of TP53 being a frameshift region mutation of amino acids 27 to 330 and / or a nonsense mutation of amino acids 94 to 342 and / or a missense mutation of amino acids 110 to 337; The TP53 deleterious mutations optionally include ATM, AR, APC, BRIP1, BRCA1, BTK, UGT1A1, CTNNB1, CDH1, PIK3CA, RB1, MLH1, FOXL2, PTCH1, TERT, RAD51C, RB1, NF1, RAF1, ERBB4, MUTYH, PALB2, CDKN2A, VEGFA, TSC1, CHEK2, PIK3R1, PDGFRA, POLE, SMAD4, BRCA2, PTEN, NBN, NTRK1, MPL, IDH2, CHEK2, TSHR, PALB2 mutations; Furthermore, the TP53 deleterious mutation is preferably selected from any one of the following schemes: Scheme 1 ATM:NM_000051.3:exon51:c.7629+1G>A:-:-; and TP53:NM_000546.5:exon5:c.493C>T:p.Gln165*:p.Q165X; and UGT1A1:NM_000463.3:exon1:c.686C>A:p.Pro229Gln:p.P229Q; Scheme 2 CTNNB1:NM_001904.4:exon3:c.122C>T:p.Thr41Ile:p.T41I; and PIK3CA:NM_006218.4:exon10:c.1633G>A:p.Glu545Lys:p.E545K; and RB1:NM_000321.2:exon23:c.2359C>T:p.Arg787*:p.R787X; and TP53:NM_000546.5:exon7:c.782+1G>A:-:-; Scheme 3 ATM:NM_000051.3:exon5:c.496+1G>A:-:-; and TP53:NM_000546.5:exon4:c.216dupC:p.Val73fs:p.V73Rfs*76; Scheme 4 TP53:NM_000546.5:exon6:c.661G>T:p.Glu221*:p.E221X; Scheme 5 TP53:NM_000546.5:exon8:c.848G>C:p.Arg283Pro:p.R283P; Scheme 6 TP53:NM_000546.5:exon7:c.718A>C:p.Ser240Arg:p.S240R; Scheme 7 TP53:NM_000546.5:exon7:c.730G>A:p.Gly244Ser:p.G244S; Scheme 8 TP53:NM_000546.5:exon6:c.638G>A:p.Arg213Gln:p.R213Q; Scheme 9 APC:NM_000038.6:exon8:c.835-8A>G:-:-; and BRIP1:NM_032043.3:exon7:c.918+1G>A:-:-; and TP53:NM_000546.5:exon7:c.733G>A:p.Gly245Ser:p.G245S; and UGT1A1:NM_000463.3:exon1:c.686C>A:p.Pro229Gln:p.P229Q; Scheme 10 TP53:NM_000546.5:exon5:c.413C>T:p.Ala138Val:p.A138V; Scheme 11 CTNNB1:NM_001904.4:exon3:c.98C>T:p.Ser33Phe:p.S33F; and TP53:NM_000546.5:exon8:c.817C>T:p.Arg273Cys:p.R273C; Scheme 12 BRCA1:NM_007294.4:exon6:c.329dupA:p.Glu111fs:p.E111Gfs*3; and CDH1:NM_004360.5:exon9:c.1212delC:p.Asn405fs:p.N405Ifs*12; and TP53:NM_000546.5:exon4:c.216dupC:p.Val73fs:p.V73Rfs*76; Scheme 13 TP53:NM_000546.5:exon5:c.517G>T:p.Val173Leu:p.V173L; Scheme 14 APC:NM_000038.6:exon16:c.4348C>T:p.Arg1450*:p.R1450X; and APC:NM_000038.6:exon16:c.4393_4394delAG:p.Ser1465fs:p.S1465Wfs*3; and MLH1:NM_000249.3:exon10:c.793C>T:p.Arg265Cys:p.R265C; and TP53:NM_000546.5:exon8:c.797G>T:p.Gly266Val:p.G266V; Scheme 15 TP53:NM_000546.5:exon5:c.524G>T:p.Arg175Leu:p.R175L; Scheme 16 TP53:NM_000546.5:exon7:c.737T>A:p.Met246Lys:p.M246K; Scheme 17 FOXL2:NM_023067.4:exon1:c.1045C>G:p.Arg349Gly:p.R349G; and PTCH1:NM_000264.5:exon14:c.2178dupC:p.Cys727fs:p.C727Lfs*11; and TP53:NM_000546.5:exon6:c.644G>T:p.Ser215Ile:p.S215I; Scheme 18 SMAD4:NM_005359.6:exon9:c.1082G>A:p.Arg361His:p.R361H; and TP53:NM_000546.5:exon8:c.811G>A:p.Glu271Lys:p.E271K; Scheme 19 TP53:NM_000546.5:exon8:c.818G>A:p.Arg273His:p.R273H; Scheme 20 TP53:NM_000546.5:exon7:c.701A>G:p.Tyr234Cys:p.Y234C; Scheme 21 PIK3CA:NM_006218.4:exon10:c.1633G>A:p.Glu545Lys:p.E545K; and TP53:NM_000546.5:exon5:c.527G>T:p.Cys176Phe:p.C176F; Scheme 22 CHEK2:NM_007194.4:exon12:c.1355G>A:p.Trp452*:p.W452X; and RAD51D:NM_002878.3:exon4:c.345+1G>A:-:-; and TP53:NM_000546.5:exon8:c.844C>T:p.Arg282Trp:p.R282W; Scheme 23 ATM:NM_000051.3:exon42:c.6100C>T:p.Arg2034*:p.R2034X; and TP53:NM_000546.5:exon5:c.413C>T:p.Ala138Val:p.A138V; and TP53:NM_000546.5:exon8:c.833C>T:p.Pro278Leu:p.P278L; and TSC2:NM_000548.5:exon21:c.2355+1G>A:-:-; Scheme 24 TERT:NM_198253.3:exon-:c.-124C>T:-:-; and TP53:NM_000546.5:exon7:c.730G>T:p.Gly244Cys:p.G244C; Scheme 25 CTNNB1:NM_001904.4:exon3:c.110C>G:p.Ser37Cys:p.S37C; and SMAD4:NM_005359.6:exon9:c.1082G>A:p.Arg361His:p.R361H; and TP53:NM_000546.5:exon8:c.853G>A:p.Glu285Lys:p.E285K; Scheme 26 APC:NM_000038.6:exon12:c.1548+1G>A:-:-; and AR:NM_000044.6:exon7:c.2599G>A:p.Val867Met:p.V867M; and RAD51C:NM_058216.3:exon5:c.709C>T:p.Arg237*:p.R237X; and RB1:NM_000321.2:exon13:c.1332+1G>A:-:-; and RB1:NM_000321.2:exon19:c.1960+1G>T:-:-; and TP53:NM_000546.5:exon5:c.430C>T:p.Gln144*:p.Q144X; Scheme 27 TP53:NM_000546.5:exon5:c.481G>A:p.Ala161Thr:p.A161T; Scheme 28 TP53:NM_000546.5:exon8:c.814G>A:p.Val272Met:p.V272M; Scheme 29 TP53:NM_000546.5:exon4:c.159G>A:p.Trp53*:p.W53X; Scheme 30 TP53:NM_000546.5:exon8:c.814G>T:p.Val272Leu:p.V272L; Scheme 31 PIK3CA:NM_006218.4:exon5:c.1030G>A:p.Val344Met:p.V344M; and TP53:NM_000546.5:exon7:c.742C>T:p.Arg248Trp:p.R248W; Scheme 32 TP53:NM_000546.5:exon7:c.761T>C:p.Ile254Thr:p.I254T; Scheme 33 CTNNB1:NM_001904.4:exon3:c.110C>G:p.Ser37Cys:p.S37C; and TP53:NM_000546.5:exon8:c.853G>A:p.Glu285Lys:p.E285K; and TP53:NM_000546.5:exon5:c.518T>C:p.Val173Ala:p.V173A; Scheme 34 TP53:NM_000546.5:exon6:c.626_627delGA:p.Arg209fs:p.R209Kfs*6; Scheme 35 TP53:NM_000546.5:exon4:c.298C>T:p.Gln100*:p.Q100X; Scheme 36 PIK3CA:NM_006218.4:exon2:c.323G>A:p.Arg108His:p.R108H; and TP53:NM_000546.5:exon5:c.541C>T:p.Arg181Cys:p.R181C; Scheme 37 NF1:NM_001042492.3:exon12:c.1381C>T:p.Arg461*:p.R461X; and RAF1:NM_002880.3:exon7:c.770C>T:p.Ser257Leu:p.S257L; and RB1:NM_000321.2:exon20:c.2107-1G>C:-:-; and TP53:NM_000546.5:exon5:c.524G>A:p.Arg175His:p.R175H; Scheme 38 ERBB4:NM_005235.3:exon2:c.119_120delCT:p.Ser40fs:p.S40*; and TP53:NM_000546.5:exon5:c.473G>T:p.Arg158Leu:p.R158L; and VHL:NM_000551.3:exon3:c.482G>A:p.Arg161Gln:p.R161Q; Scheme 39 TP53:NM_000546.5:exon6:c.659A>G:p.Tyr220Cys:p.Y220C; Scheme 40 TP53:NM_000546.5:exon6:c.577C>T:p.His193Tyr:p.H193Y; Scheme 41 BRCA2:NM_000059.3:exon15:c.7522G>A:p.Gly2508Ser:p.G2508S; and TP53:NM_000546.5:exon5:c.538G>A:p.Glu180Lys:p.E180K; Scheme 42 MUTYH:NM_001128425.1:exon10:c.934-2A>G:-:-; and PALB2:NM_024675.4:exon4:c.1213C>G:p.Pro405Ala:p.P405A; and TP53:NM_000546.5:exon6:c.646G>A:p.Val216Met:p.V216M; Scheme 43 TP53:NM_000546.5:exon5:c.527G>A:p.Cys176Tyr:p.C176Y; Scheme 44 CDKN2A:NM_000077.4:exon1:c.32dupC:p.Ser12fs:p.S12Ffs*3; and TP53:NM_000546.5:exon9:c.991C>T:p.Gln331*:p.Q331X; Scheme 45 TP53:NM_000546.5:exon7:c.783-1G>T:-:-; and VEGFA:NM_001025366.3:exon1:c.19_22dupGACA:p.Thr8fs:p.T8Rfs*78; Scheme 46 TP53:NM_000546.5:exon5:c.503A>G:p.His168Arg:p.H168R; Scheme 47 CTNNB1:NM_001904.4:exon3:c.101G>T:p.Gly34Val:p.G34V; and TP53:NM_000546.5:exon8:c.817C>T:p.Arg273Cys:p.R273C; and TSC1:NM_000368.5:exon15:c.1498C>T:p.Arg500*:p.R500X; Scheme 48 TP53:NM_000546.5:exon8:c.841G>C:p.Asp281His:p.D281H; and UGT1A1:NM_000463.3:exon1:c.686C>A:p.Pro229Gln:p.P229Q; Scheme 49 ATM:NM_000051.3:exon46:c.6807G>A:p.Gln2269Gln:p.Q2269Q; and CHEK2:NM_007194.4:exon3:c.409C>T:p.Arg137*:p.R137X; and CTNNB1:NM_001904.4:exon3:c.98C>G:p.Ser33Cys:p.S33C; and PIK3R1:NM_181523.3:exon11:c.1425+1G>A:-:-; and TP53:NM_000546.5:exon5:c.532delC:p.His178fs:p.H178Tfs*69; and TSC1:NM_000368.5:exon17:c.2074C>T:p.Arg692*:p.R692X; Scheme 50 TP53:NM_000546.5:exon6:c.644G>T:p.Ser215Ile:p.S215I; and BRCA2:NM_000059.3:exon5:c.475+3A>G:-:-; and BTK:NM_000061.2:exon15:c.1455C>A:p.Tyr485*:p.Y485X; and TP53:NM_000546.5:exon9:c.994-1G>A:-:-; Scheme 51 PDGFRA:NM_006206.6:exon22:c.3098A>T:p.Asp1033Val:p.D1033V; and TP53:NM_000546.5:exon5:c.527G>T:p.Cys176Phe:p.C176F; Scheme 52 TP53:NM_000546.5:exon7:c.743G>T:p.Arg248Leu:p.R248L; Scheme 53 TP53:NM_000546.5:exon7:c.743G>A:p.Arg248Gln:p.R248Q; Scheme 54 TP53:NM_000546.5:exon10:c.1024C>T:p.Arg342*:p.R342X; Scheme 55 TP53:NM_000546.5:exon4:c.374C>T:p.Thr125Met:p.T125M; and TP53:NM_000546.5:exon8:c.853G>A:p.Glu285Lys:p.E285K; and TP53:NM_000546.5:exon8:c.839G>C:p.Arg280Thr:p.R280T; Scheme 56 POLE:NM_006231.4:exon5:c.424-1G>A:-:-; and SMAD4:NM_005359.6:exon9:c.1082G>A:p.Arg361His:p.R361H; and TP53:NM_000546.5:exon6:c.641A>G:p.His214Arg:p.H214R; Scheme 57 TP53:NM_000546.5:exon5:c.421T>C:p.Cys141Arg:p.C141R; Scheme 58 TP53:NM_000546.5:exon5:c.422G>A:p.Cys141Tyr:p.C141Y; Scheme 59 TP53:NM_000546.5:exon8:c.920-2A>G:-:-; Scheme 60 BRCA2:NM_000059.3:exon15:c.7522G>A:p.Gly2508Ser:p.G2508S; and PIK3CA:NM_006218.4:exon21:c.3129G>T:p.Met1043Ile:p.M1043I; and TP53:NM_000546.5:exon7:c.743G>A:p.Arg248Gln:p.R248Q; Scheme 61 MUTYH:NM_001128425.1:exon10:c.934-2A>G:-:-; and TP53:NM_000546.5:exon4:c.376-1G>A:-:-; Scheme 62 TP53:NM_000546.5:exon5:c.398T>C:p.Met133Thr:p.M133T Scheme 63 TP53:NM_000546.5:exon5:c.469G>T:p.Val157Phe:p.V157F; and TP53:NM_000546.5:exon6:c.638G>A:p.Arg213Gln:p.R213Q; and TP53:NM_000546.5:exon5:c.527G>T:p.Cys176Phe:p.C176F; Scheme 64 TP53:NM_000546.5:exon4:c.102delC:p.Leu35fs:p.L35Cfs*9; Scheme 65 TP53:NM_000546.5:exon8:c.832C>A:p.Pro278Thr:p.P278T; Scheme 66 TP53:NM_000546.5:exon9:c.988delC:p.Leu330fs:p.L330Ffs*15; and PTEN:NM_000314.8:exon6:c.511C>G:p.Gln171Glu:p.Q171E; and TP53:NM_000546.5:exon8:c.844C>G:p.Arg282Gly:p.R282G; Scheme 67 APC:NM_000038.6:exon16:c.2299C>T:p.Gln767*:p.Q767X; and TP53:NM_000546.5:exon6:c.659A>G:p.Tyr220Cys:p.Y220C; Scheme 68 PTEN:NM_000314.8:exon9:c.1211G>C:p.Ter404Serext*:p.X404S; and TP53:NM_000546.5:exon3:c.80delC:p.Pro27fs:p.P27Lfs*17; Scheme 69 ATM:NM_000051.3:exon55:c.8071C>T:p.Arg2691Cys:p.R2691C; and RB1:NM_000321.2:exon2:c.219_220delAG:p.Arg73fs:p.R73Sfs*36; and TP53:NM_000546.5:exon8:c.818G>C:p.Arg273Pro:p.R273P; Scheme 70 TP53:NM_000546.5:exon7:c.725G>T:p.Cys242Phe:p.C242F; Scheme 71 TP53:NM_000546.5:exon7:c.734G>A:p.Gly245Asp:p.G245D; Scheme 72 CTNNB1:NM_001904.4:exon3:c.98C>G:p.Ser33Cys:p.S33C; and CTNNB1:NM_001904.4:exon3:c.110C>A:p.Ser37Tyr:p.S37Y; TP53:NM_000546.5:exon5:c.455C>T:p.Pro152Leu:p.P152L; Scheme 73 TP53:NM_000546.5:exon7:c.745A>T:p.Arg249Trp:p.R249W; and VEGFA:NM_001025366.3:exon1:c.19_22dupGACA:p.Thr8fs:p.T8Rfs*78; Scheme 74 TP53:NM_000546.5:exon4:c.281C>A:p.Ser94*:p.S94X; Scheme 75 TP53:NM_000546.5:exon7:c.776A>T:p.Asp259Val:p.D259V; Scheme 76 AR:NM_000044.6:exon1:c.902A>G:p.Lys301Arg:p.K301R; and TP53:NM_000546.5:exon5:c.464C>A:p.Thr155Asn:p.T155N; Scheme 77 TP53:NM_000546.5:exon5:c.389T>A:p.Leu130His:p.L130H; Scheme 78 TP53:NM_000546.5:exon5:c.404G>T:p.Cys135Phe:p.C135F; Scheme 79 TP53:NM_000546.5:exon5:c.451C>T:p.Pro151Ser:p.P151S; Scheme 80 TP53:NM_000546.5:exon8:c.823T>C:p.Cys275Arg:p.C275R; Scheme 81 FOXL2:NM_023067.4:exon1:c.1045C>G:p.Arg349Gly:p.R349G; and TP53:NM_000546.5:exon6:c.615T>A:p.Tyr205*:p.Y205X; Scheme 82 BRCA1:NM_007294.4:exon10:c.1465G>T:p.Glu489*:p.E489X; and FOXL2:NM_023067.4:exon1:c.1045C>G:p.Arg349Gly:p.R349G; and NBN:NM_002485.4:exon1:c.3G>A:p.Met1:p.M1; and NTRK1:NM_002529.3:exon14:c.1768G>A:p.Glu590Lys:p.E590K; and TP53:NM_000546.5:exon9:c.949C>T:p.Gln317*:p.Q317X; Scheme 83 MPL:NM_005373.3:exon3:c.235_236delCT:p.Leu79fs:p.L79Efs*84; and TP53:NM_000546.5:exon6:c.646G>T:p.Val216Leu:p.V216L; Scheme 84 TP53:NM_000546.5:exon5:c.535C>G:p.His179Asp:p.H179D; and UGT1A1:NM_000463.3:exon1:c.686C>A:p.Pro229Gln:p.P229Q Scheme 85 TP53:NM_000546.5:exon7:c.742C>T:p.Arg248Trp:p.R248W; Scheme 86 TP53:NM_000546.5:exon3:c.97-1G>A:-:-; Scheme 87 TP53:NM_000546.5:exon5:c.455C>G:p.Pro152Arg:p.P152R; Scheme 88 TP53:NM_000546.5:exon9:c.993+1G>T:-:-; Scheme 89 TP53:NM_000546.5:exon7:c.707A>G:p.Tyr236Cys:p.Y236C; Scheme 90 CTNNB1:NM_001904.4:exon3:c.100G>A:p.Gly34Arg:p.G34R; and TP53:NM_000546.5:exon4:c.159G>A:p.Trp53*:p.W53X; Scheme 91 TP53:NM_000546.5:exon8:c.818G>A:p.Arg273His:p.R273H; Scheme 92 ATM:NM_000051.3:exon49:c.7141_7151delAATGGAAAAAT:p.Asn2381fs:p.N2381Efs*18; and TP53:NM_000546.5:exon7:c.743G>A:p.Arg248Gln:p.R248Q; Scheme 93 TP53:NM_000546.5:exon8:c.830G>T:p.Cys277Phe:p.C277F; Scheme 94 TP53:NM_000546.5:exon8:c.841G>C:p.Asp281His:p.D281H; Scheme 95 TP53:NM_000546.5:exon5:c.469G>T:p.Val157Phe:p.V157F; Scheme 96 NTRK1:NM_002529.3:exon17:c.2303C>T:p.Pro768Leu:p.P768L; and TP53:NM_000546.5:exon5:c.388C>T:p.Leu130Phe:p.L130F; Scheme 97 TP53:NM_000546.5:exon5:c.403T>C:p.Cys135Arg:p.C135R; Scheme 98 NF1:NM_001042492.3:exon33:c.4339C>T:p.Gln1447*:p.Q1447X; and TP53:NM_000546.5:exon9:c.927delC:p.Asn310fs:p.N310Tfs*35; Scheme 99 SF3B1:NM_012433.3:exon14:c.1998G>C:p.Lys666Asn:p.K666N; and TP53:NM_000546.5:exon4:c.375+1G>T:-:-; Scheme 100 TP53:NM_000546.5:exon6:c.637C>T:p.Arg213*:p.R213X; Scheme 101 TP53:NM_000546.5:exon4:c.154C>T:p.Gln52*:p.Q52X; Scheme 102 IDH2:NM_002168.3:exon4:c.419G>A:p.Arg140Gln:p.R140Q; and PIK3CA:NM_006218.4:exon10:c.1633G>A:p.Glu545Lys:p.E545K; and TP53:NM_000546.5:exon10:c.1010G>A:p.Arg337His:p.R337H; Scheme 103 TP53:NM_000546.5:exon4:c.310C>T:p.Gln104*:p.Q104X; Scheme 104 BRCA2:NM_000059.3:exon15:c.7522G>A:p.Gly2508Ser:p.G2508S; and TP53:NM_000546.5:exon10:c.1024C>T:p.Arg342*:p.R342X; Scheme 105 TP53:NM_000546.5:exon6:c.673-1G>T:-:-; Scheme 106 TP53:NM_000546.5:exon8:c.836G>A:p.Gly279Glu:p.G279E; Scheme 107 RB1:NM_000321.2:exon2:c.142G>T:p.Glu48*:p.E48X; and TP53:NM_000546.5:exon8:c.919+2T>A:-:-; Scheme 108 PIK3CA:NM_006218.4:exon10:c.1624G>A:p.Glu542Lys:p.E542K; and RB1:NM_000321.2:exon8:c.751C>T:p.Arg251*:p.R251X; and TP53:NM_000546.5:exon4:c.337T>G:p.Phe113Val:p.F113V; Scheme 109 NF1:NM_001042492.3:exon33:c.4339C>G:p.Gln1447Glu:p.Q1447E; and PIK3CA:NM_006218.4:exon10:c.1633G>A:p.Glu545Lys:p.E545K; and TP53:NM_000546.5:exon8:c.856G>A:p.Glu286Lys:p.E286K; Scheme 110 PIK3CA:NM_006218.4:exon8:c.1357G>C:p.Glu453Gln:p.E453Q; and PIK3CA:NM_006218.4:exon19:c.2702G>T:p.Cys901Phe:p.C901F; and TP53:NM_000546.5:exon7:c.722C>T:p.Ser241Phe:p.S241F; Scheme 111 APC:NM_000038.6:exon5:c.481C>T:p.Gln161*:p.Q161X; and TP53:NM_000546.5:exon8:c.817C>T:p.Arg273Cys:p.R273C; Scheme 112 TP53:NM_000546.5:exon5:c.524G>A:p.Arg175His:p.R175H; Scheme 113 PIK3CA:NM_006218.4:exon10:c.1633G>A:p.Glu545Lys:p.E545K; and TP53:NM_000546.5:exon7:c.742C>G:p.Arg248Gly:p.R248G; Scheme 114 CHEK2:NM_007194.4:exon11:c.1260-1G>A:-:-; and PTEN:NM_000314.8:exon2:c.107G>A:p.Gly36Glu:p.G36E; and TP53:NM_000546.5:exon5:c.524G>A:p.Arg175His:p.R175H; Scheme 115 TP53:NM_000546.5:exon5:c.523C>G:p.Arg175Gly:p.R175G; Scheme 116 FOXL2:NM_023067.4:exon1:c.1045C>G:p.Arg349Gly:p.R349G; and PTEN:NM_000314.8:exon5:c.464A>G:p.Tyr155Cys:p.Y155C; and PTEN:NM_000314.8:exon6:c.518G>C:p.Arg173Pro:p.R173P; and TP53:NM_000546.5:exon10:c.1024C>T:p.Arg342*:p.R342X; and TSHR:NM_000369.3:exon10:c.1574T>C:p.Phe525Ser:p.F525S; Scheme 117 TP53:NM_000546.5:exon5:c.404G>A:p.Cys135Tyr:p.C135Y; Scheme 118 APC:NM_000038.6:exon16:c.2926delA:p.Arg976fs:p.R976Efs*4; and FOXL2:NM_023067.4:exon1:c.1045C>G:p.Arg349Gly:p.R349G; and PALB2:NM_024675.4:exon5:c.2038G>T:p.Gly680*:p.G680X; and TP53:NM_000546.5:exon7:c.734G>T:p.Gly245Val:p.G245V; and TSHR:NM_000369.3:exon10:c.1574T>C:p.Phe525Ser:p.F525S; Scheme 119 TP53:NM_000546.5:exon7:c.746G>A:p.Arg249Lys:p.R249K; Scheme 120 PIK3CA:NM_006218.4:exon10:c.1624G>C:p.Glu542Gln:p.E542Q; and TP53:NM_000546.5:exon6:c.638G>C:p.Arg213Pro:p.R213P; Scheme 121 TP53:NM_000546.5:exon6:c.578A>G:p.His193Arg:p.H193R; Scheme 122 RB1:NM_000321.2:exon21:c.2211+5G>A:-:-; and TP53:NM_000546.5:exon8:c.817C>T:p.Arg273Cys:p.R273C; Scheme 123 TP53:NM_000546.5:exon7:c.718A>G:p.Ser240Gly:p.S240G; Scheme 124 TP53:NM_000546.5:exon10:c.1009C>T:p.Arg337Cys:p.R337C; Scheme 125 TP53:NM_000546.5:exon7:c.783-2A>C:-:-; Scheme 126 BRCA2:NM_000059.3:exon21:c.8702G>A:p.Gly2901Asp:p.G2901D; and TP53:NM_000546.5:exon5:c.499C>T:p.Gln167*:p.Q167X; Scheme 127 TP53:NM_000546.5:exon3:c.97-2delA:-:-; Scheme 128 TP53:NM_000546.5:exon4:c.329G>T:p.Arg110Leu:p.R110L. In some embodiments, the combined deleterious mutations are tested by conventional gene sequencing methods in the art, such as high-throughput sequencing, for example, high-throughput sequencing on the Illumina MiseqDx / CN500 platform. In some embodiments, the genetic sample is isolated from saliva, blood, urine, malignant tissue exudate, or tumor tissue, preferably the genomic sample is isolated from tumor tissue. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is prepared into a clinically acceptable formulation, such as a tablet formulation. In some embodiments, the administration frequency of the compound represented by Formula I or a pharmaceutically acceptable salt thereof is conventional in the art, preferably once per day. In some embodiments, the dosage of the compound of Formula I or a pharmaceutically acceptable salt thereof is 40-80 mg, preferably 40 mg, 45 mg, 50 mg, 60 mg, 65 mg, 70 mg or 80 mg, and more preferably 60 mg. In some embodiments, the treatment time of the compound of Formula I or a pharmaceutically acceptable salt thereof is greater than 7.2 months, preferably greater than 12.9 months, and further preferably greater than 23.9 months, thereby prolonging the subject's survival, including progression-free survival. For example, the progression-free survival is preferably greater than 6.9 months, further preferably greater than 12.6 months, and further preferably greater than 23.4 months. In some embodiments, the treatment time of the compound of Formula I or a pharmaceutically acceptable salt thereof is greater than 7.2 months, preferably greater than 12.9 months, and further preferably greater than 23.9 months, thereby prolonging the subject's survival, including overall survival, for example, the overall survival is preferably greater than 18.8 months, and further preferably greater than 30.4 months. In some preferred embodiments, a compound having a structure of formula I or a pharmaceutically acceptable salt thereof is provided for use in the preparation of a compound for treating EGFR L858R Use in a drug for treating one or more diseases associated with harmful mutations, The treatment duration of the compound of Formula I or a pharmaceutically acceptable salt thereof is greater than 7.2 months, preferably greater than 12.9 months, and further preferably greater than 23.9 months, thereby prolonging the subject's survival, including progression-free survival, for example, the progression-free survival is preferably greater than 6.9 months, further preferably greater than 13.7 months, and further preferably greater than 20.7 months; Among them, the treatment time of the compound represented by Formula I or a pharmaceutically acceptable salt thereof is greater than 7.2 months, preferably greater than 12.9 months, and further preferably greater than 23.9 months, thereby prolonging the survival of the subject, including the overall survival, for example, the overall survival is preferably greater than 18.2 months, and further preferably greater than 29.1 months. In some preferred embodiments, a compound having a structure of formula I or a pharmaceutically acceptable salt thereof is provided for use in the preparation of a compound for treating EGFR 19DELUse in a drug for treating one or more diseases associated with harmful mutations, The treatment duration of the compound of Formula I or a pharmaceutically acceptable salt thereof is greater than 7.2 months, preferably greater than 12.9 months, and further preferably greater than 23.9 months, thereby prolonging the subject's survival, including progression-free survival, for example, the progression-free survival is preferably greater than 6.9 months, further preferably greater than 12.6 months, and further preferably greater than 23.5 months; Among them, the treatment time of the compound represented by Formula I or a pharmaceutically acceptable salt thereof is greater than 7.2 months, preferably greater than 12.9 months, and further preferably greater than 23.9 months, thereby prolonging the survival of the subject, including the overall survival, for example, the overall survival is preferably greater than 19.8 months, and further preferably greater than 28.2 months. In some preferred embodiments, a compound having a structure of Formula I or a pharmaceutically acceptable salt thereof is provided for use in preparing a drug for treating a disease associated with EGFR combined with TP53 deleterious mutations. The treatment duration of the compound of Formula I or a pharmaceutically acceptable salt thereof is greater than 7.2 months, preferably greater than 12.9 months, and further preferably greater than 23.9 months, thereby prolonging the subject's survival, including progression-free survival, for example, the progression-free survival is preferably greater than 6.9 months, further preferably greater than 12.4 months, and further preferably greater than 17.9 months; Among them, the treatment time of the compound represented by Formula I or a pharmaceutically acceptable salt thereof is greater than 7.2 months, preferably greater than 12.9 months, and further preferably greater than 23.9 months, thereby prolonging the survival of the subject, including the overall survival, for example, the overall survival is preferably greater than 18.2 months, and further preferably greater than 29.1 months. In some preferred embodiments, a compound having a structure of formula I or a pharmaceutically acceptable salt thereof is provided for use in the preparation of a compound for treating EGFR L858R Use in drugs for diseases associated with TP53 deleterious mutations, The treatment duration of the compound of Formula I or a pharmaceutically acceptable salt thereof is greater than 7.2 months, preferably greater than 12.9 months, and further preferably greater than 23.9 months, thereby prolonging the subject's survival, including progression-free survival. For example, the progression-free survival is preferably greater than 6.8 months, further preferably greater than 11.9 months, and further preferably greater than 17.9 months. Among them, the treatment time of the compound represented by Formula I or a pharmaceutically acceptable salt thereof is greater than 7.2 months, preferably greater than 12.9 months, and further preferably greater than 23.9 months, thereby prolonging the survival of the subject, including the overall survival, for example, the overall survival is preferably greater than 16.9 months, and further preferably greater than 30.4 months. In some preferred embodiments, a compound having a structure of formula I or a pharmaceutically acceptable salt thereof is provided for use in the preparation of a compound for treating EGFR 19DEL Use in drugs for diseases associated with TP53 deleterious mutations, Wherein, the treatment time of the compound represented by Formula I or a pharmaceutically acceptable salt thereof is greater than 7.2 months, preferably greater than 12.9 months, and further preferably greater than 23.9 months, thereby prolonging the survival of the subject, including progression-free survival, for example, the progression-free survival is preferably greater than 8.3 months, further preferably greater than 12.6 months, and further preferably greater than 22.0 months; Among them, the treatment time of the compound represented by Formula I or a pharmaceutically acceptable salt thereof is greater than 7.2 months, preferably greater than 12.9 months, and further preferably greater than 23.9 months, thereby prolonging the survival of the subject, including the overall survival, for example, the overall survival is preferably greater than 20.2 months, and further preferably greater than 28.2 months. The second aspect of the present invention is to provide a method for treating or preventing diseases mediated by EGFR mutations combined with one or more deleterious mutations, the method comprising administering to a subject a therapeutically effective amount of compound I or a pharmaceutically acceptable salt thereof, wherein the compound of formula I, the pharmaceutically acceptable salt, the disease, the drug, and the EGFR mutation combined with one or more deleterious mutations are as described above. In a third aspect of the present invention, provided is the use of a compound of Formula I or a pharmaceutically acceptable salt thereof in the preparation of a drug for improving survival in patients with EGFR-mutated non-small cell lung cancer combined with one or more deleterious mutations, wherein the drug is a drug for treating diseases associated with EGFR mutations combined with one or more deleterious mutations, wherein the compound of Formula I, the pharmaceutically acceptable salt, the disease, the EGFR mutation, the deleterious mutation, and the drug are as described above. In a fourth aspect of the present invention, a method for prolonging progression-free survival of a subject is provided, wherein the method comprises administering a therapeutically effective amount of a compound of Formula I to the subject, wherein the compound of Formula I, the pharmaceutically acceptable salt, the disease, the drug, the EGFR mutation combined with the deleterious mutation, and the therapeutically effective amount are defined as described above. In a fifth aspect of the present invention, there is provided the use of the compound represented by the above formula I in the preparation of a combination therapeutic drug for patients with a disease, wherein the disease is non-small cell lung cancer, preferably non-small cell lung cancer associated with the above-mentioned EGFR mutation combined with deleterious mutations. In some embodiments, the patient is a human with histologically or cytologically confirmed locally advanced or metastatic non-squamous non-small cell lung cancer. A sixth aspect of the present invention provides a combined treatment method for patients with non-small cell lung cancer, comprising the following steps: 1) assessing the presence of at least one EGFR mutation combined with the above-mentioned deleterious mutations in a biological sample from the patient; 2) Performing combination therapy of the compound represented by formula I and an inhibitor targeting the above-mentioned deleterious mutation on patients suitable for combination therapy. In some embodiments, the patient is a human with histologically or cytologically confirmed locally advanced or metastatic non-squamous non-small cell lung cancer. Definition of terms Unless otherwise specified, all technical and scientific terms used herein have the standard meanings in the art to which the claimed subject matter belongs. In the event that multiple definitions exist for a term, the definition herein shall prevail. When reference is made to a URL or other identifier or address, it should be understood that such identifiers may change, and specific information on the internet may change, but equivalent information can be found by searching the internet. Such reference provides evidence that such information is available and publicly disseminated. The term "pharmaceutically acceptable" as used in the present invention refers to those compounds, materials, compositions and / or dosage forms that are, within the scope of sound medical judgment, suitable for use in contact with human and animal tissues without excessive toxicity, irritation, allergic response or other problems or complications, commensurate with a reasonable benefit / risk ratio. The term "pharmaceutically acceptable salt" refers to salts of the compounds of the present invention, prepared by reacting the compounds of the present invention with relatively nontoxic acids or bases, having specific substituents. When the compounds of the present invention contain relatively acidic functional groups, base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of base in neat solution or in a suitable inert solvent. Pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amino or magnesium salts, or similar salts. When compounds of the present invention contain relatively basic functionalities, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of acid, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include inorganic acid salts such as hydrochloric acid, hydrobromic acid, nitric acid, carbonic acid, bicarbonate, phosphoric acid, monohydrogen phosphate, dihydrogen phosphate, sulfuric acid, bisulfate, hydroiodic acid, phosphorous acid, and the like; and organic acid salts such as acetic acid, propionic acid, isobutyric acid, maleic acid, malonic acid, benzoic acid, succinic acid, suberic acid, fumaric acid, lactic acid, mandelic acid, phthalic acid, benzenesulfonic acid, p-toluenesulfonic acid, citric acid, tartaric acid, and methanesulfonic acid; and salts of amino acids such as arginine, and organic acids such as glucuronic acid (see Berge et al., "Pharmaceutical Salts", Journal of Pharmaceutical Science 66: 1-19 (1977)). Certain specific compounds of the present invention contain both basic and acidic functional groups and can be converted into either base or acid addition salts. Preferably, the neutral form of the compound is regenerated by contacting the salt with a base or acid in a conventional manner and isolating the parent compound. The parent form of the compound differs from its various salt forms in certain physical properties, such as solubility in polar solvents. As used herein, "pharmaceutically acceptable salts" are derivatives of the compounds of the present invention wherein the parent compound is modified by acid or base salt formation. Examples of pharmaceutically acceptable salts include, but are not limited to, inorganic or organic acid salts of bases such as amines, alkali metal or organic salts of acid radicals such as carboxylic acids, and the like. Pharmaceutically acceptable salts include conventional non-toxic salts or quaternary ammonium salts of the parent compound, such as salts formed with non-toxic inorganic or organic acids. Conventional non-toxic salts include, but are not limited to, those derived from inorganic and organic acids selected from 2-acetoxybenzoic acid, 2-hydroxyethanesulfonic acid, acetic acid, ascorbic acid, benzenesulfonic acid, benzoic acid, bicarbonate, carbonic acid, citric acid, edetic acid, ethanedisulfonic acid, ethanesulfonic acid, fumaric acid, glucoheptose, gluconic acid, glutamic acid, glycolic acid, hydrobromic acid, hydrochloric acid, hydroiodide, hydroxynaphthalene, isethionic acid, lactic acid, lactose, dodecylsulfonic acid, maleic acid, malic acid, mandelic acid, methanesulfonic acid, nitric acid, oxalic acid, pamoic acid, pantothenic acid, phenylacetic acid, phosphoric acid, propionic acid, salicylic acid, stearic acid, acetic acid, succinic acid, sulfamic acid, p-aminobenzenesulfonic acid, sulfuric acid, tannin, tartaric acid, and p-toluenesulfonic acid. The "pharmaceutically acceptable salts" of the present invention can be synthesized from parent compounds containing acid or basic groups by conventional chemical methods. Generally, such salts are prepared by reacting the free acid or base form of these compounds with a stoichiometric amount of an appropriate base or acid in water or an organic solvent, or a mixture of the two. Generally, non-aqueous media such as ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. In addition to the form of salts, the compounds provided by the present invention also exist in prodrug form. The prodrugs of the compounds described herein are easily chemically changed under physiological conditions to be converted into the compounds of the present invention. Any compound that can be converted in vivo to provide a bioactive substance (i.e., compound shown in Formula I) is a prodrug within the scope and spirit of the present invention. For example, a compound containing a carboxyl group can form a physiologically hydrolyzable ester, which acts as a prodrug by being hydrolyzed in vivo to obtain the compound shown in Formula I itself. The prodrug is preferably administered orally, because hydrolysis occurs mainly under the influence of digestive enzymes in many cases. When the ester itself is active or hydrolysis occurs in the blood, parenteral administration can be used. In addition, prodrugs can be converted to the compounds of the present invention by chemical or biochemical methods in an in vivo environment. With respect to a drug or pharmacologically active agent, the term "effective amount" or "therapeutically effective amount" refers to a non-toxic amount of the drug or agent sufficient to achieve the intended effect. For the oral dosage forms of the present invention, an "effective amount" of an active substance in the composition means the amount required to achieve the intended effect when used in combination with another active substance in the composition. The determination of an effective amount varies from person to person, depending on the age and general condition of the recipient, as well as the specific active substance. The appropriate effective amount in each individual case can be determined by those skilled in the art through routine experimentation. The term "comprising" is an open expression, that is, including the contents specified in the present invention, but not excluding other contents. The terms "treat," "treatment," or "therapy" as used herein include alleviating, inhibiting, or ameliorating the symptoms of a disease or condition; inhibiting the development of complications; ameliorating or preventing underlying metabolic syndrome; inhibiting the development of a disease or symptom, such as controlling the progression of a disease or condition; alleviating a disease or symptom; causing a regression of a disease or symptom; alleviating complications caused by a disease or symptom, or preventing or treating signs caused by a disease or symptom. As used herein, a compound or pharmaceutical composition, upon administration, can improve a disease, symptom, or condition, particularly by improving its severity, delaying its onset, slowing its progression, or reducing its duration. Whether the administration is fixed or temporary, continuous or intermittent, the circumstances attributable to or related to the administration can be explained. The term "progression-free survival" (PFS) was assessed by an independent review committee (IRC) according to RECIST v1.1. PFS was defined as the time (in months) from the date of treatment receipt to the first observation of disease progression (based on imaging). For subjects who died from other causes before disease progression, the time (in months) from the date of treatment receipt to death was calculated. mPFS was defined as the median progression-free survival among subjects. The term "overall survival" (OS) is defined as the time from randomization to death due to any cause (the last follow-up date for subjects lost to follow-up; the end of follow-up date for subjects still alive at the end of the study). The term "gene" refers to a human gene, which is the most basic physical and functional unit of genetic information in the genome. The term "dummy tablet" or "placebo tablet" is used in double-blind clinical trials to ensure that subjects and researchers cannot discern the specific drug being administered through sensory perception. A dummy tablet is specially prepared to resemble the study drug but without the active ingredient. This technique is known as "dummy technology." Dummy tablets are specialized research medications used exclusively in clinical studies. Their appearance (formulation, shape, color, texture), odor, and dosage are identical to the study drug, but they do not contain the drug's active ingredient. In the present invention, a compound of Formula I or a pharmaceutically acceptable salt thereof is provided, wherein the drug is administered to a subject suffering from a disease associated with an EGFR mutation combined with a deleterious mutation to obtain one or more of the following: improved progression-free survival (PFS) or improved overall survival (OS). BRIEF DESCRIPTION OF THE DRAWINGS The following drawings form part of this specification and are included to further illustrate certain aspects of the invention. The invention may be better understood by reference to one or more of these drawings in combination with the detailed description of some specific embodiments presented herein. Figure 1 shows the expression of EGFR in the Maihuatinib group. L858R Combined deleterious mutations vs EGFR in the gefitinib group L858R PFS plot for combined deleterious mutations. DETAILED DESCRIPTION The following examples are provided to better illustrate the present invention, but are not intended to limit the present invention to these examples. Any substantial improvement or adjustment to the embodiments made by those skilled in the art based on the above invention still falls within the scope of protection of the present invention. Unless expressly indicated to the contrary, the practice of the present invention will employ conventional methods of clinical medicine, clinical trials, biochemistry, and biomedical statistics within the skill of the art. List of abbreviations Example 1 A randomized, parallel-controlled, double-blind, double-dummy, multicenter phase III clinical trial of mahuatinib versus gefitinib as first-line treatment for advanced non-squamous non-small cell lung cancer with EGFR sensitive mutations Subjects: Subjects with locally advanced or metastatic non-squamous non-small cell lung cancer (including subjects with recurrence after previous radical surgical treatment or newly diagnosed stage IIIB to IV). A total of 336 subjects were actually enrolled, including 223 in the experimental group and 113 in the control group. Patients must meet all of the following inclusion criteria to be enrolled in this trial 1) Willing to sign the informed consent form; 2) Age 18-75 years old (inclusive), gender is not limited; 3) Locally advanced or metastatic non-squamous non-small cell lung cancer confirmed by histology or cytology (including subjects with recurrence after previous radical surgical treatment or newly diagnosed stage IIIB to IV. According to the AJCC 8th edition lung cancer staging criteria); 4) Have not received systemic anti-tumor treatment (for subjects who have previously received preoperative neoadjuvant chemotherapy or postoperative adjuvant chemotherapy or radical chemoradiotherapy, the time interval between the last chemotherapy and / or radiotherapy and the first receipt of study drug must be ≥ 6 months); 5) Tumor tissue samples or cell paraffin blocks confirmed by central laboratory testing to have EGFR-sensitive mutations: Ex19del or L858R (other EGFR mutation sites cannot coexist); 6) The subject must have at least one lesion with clear boundaries and reproducible measurements according to RECIST v1.1, i.e., the longest diameter must be at least 10 mm. If the CT scan slice thickness is >5 mm, the minimum lesion diameter must be twice the slice thickness. If the lesion is a lymph node, the short diameter must be at least 15 mm. The target lesion has not received radiotherapy. 7) ECOGPS physical score is 0 or 1, and there is no deterioration within two weeks before the first dose of study drug; 8) Expected survival period ≥ 3 months; 9) Laboratory indicators are basically normal: a) The absolute neutrophil count is ≥1.5×10 9 / L; b) Platelet count ≥100×109 / L; c) Hemoglobin ≥90 g / L; d) If there is no clear liver metastasis, ALT ≤ 2.5 × ULN; if there is liver metastasis, ALT ≤ 5.0 × ULN; e) If there is no clear liver metastasis, AST ≤ 2.5 × ULN; if there is liver metastasis, AST ≤ 5.0 × ULN; f) If there is no clear liver metastasis, total bilirubin ≤1.5×ULN; if there is liver metastasis, total bilirubin ≤3.0×ULN; g) Nearly normal renal function: creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 60 mL / min (using the Cockcroft-Gault method). Creatinine clearance needs to be confirmed only when creatinine is > 1.5 × ULN. h) The coagulation function is basically normal, and the INR is ≤1.5; 10) Subjects of childbearing age (both male and female) agree to use highly effective contraceptive measures (including but not limited to hormonal contraception, physical contraception, or abstinence) from the time they sign the informed consent form until at least 3 months after the last dose of study treatment. Furthermore, male subjects must not donate sperm for at least 3 months from screening until withdrawal from study treatment. Female subjects of childbearing age must not breastfeed for at least 3 months from screening until withdrawal from study treatment. Main exclusion criteria 1) Subjects with meningeal metastasis, brain metastasis, or spinal cord compression; 2) Received any of the following treatments: Previous systemic anti-tumor treatment (for subjects who have received preoperative neoadjuvant chemotherapy or postoperative adjuvant chemotherapy or radical chemoradiotherapy, the interval between the last chemotherapy and / or radiotherapy and the first study drug must be ≥6 months to be eligible for inclusion); within 4 weeks before the first dose of the study drug, received more than 30% bone marrow irradiation, or received large-area radiotherapy (except palliative radiotherapy for the purpose of relieving pain in non-target lesions, etc.), other anti-tumor therapies, including molecular targeted therapy (such as EGFR TKI, angiogenesis inhibitors, etc.), immunotherapy (such as cellular immunotherapy anti-PD-1 or anti-PD-L1), other experimental drug treatments, etc. (local treatment for malignant body fluids is eligible for inclusion); 3) Major surgery within 4 weeks before the first administration of study drug (refer to the "Surgical Classification Catalog 2011 Draft for Comments"); 4) Any Chinese medicine or Chinese patent medicine with anti-tumor effect (previous use of Chinese medicine or Chinese patent medicine with anti-tumor effect is allowed, but the drug has been discontinued for 1 week or more before treatment with this study drug); 5) The subjects are currently taking (or cannot stop taking within 1 week before the first dose of the study drug) certain drugs that are known to be strong inducers or inhibitors of cytochrome P450 (CYP2D6, CYP3A4) and P-glycoprotein (P-gp); 6) Patients who have been treated with adrenal steroids for more than two weeks continuously within 28 days before the first administration of the study drug (equivalent to a daily dose of prednisolone ≥20 mg); 7) history of interstitial lung disease, history of radiation pneumonitis requiring steroid treatment, or any evidence of clinically active interstitial lung disease; 8) Any severe or uncontrolled eye disease that, as determined by the investigator, may increase the safety risk of the subject; 9) Subjects with dysphagia or those who the investigator believes may have malabsorption disorders (clinically severe gastrointestinal dysfunction that may affect the intake, transport, or absorption of the study drug, such as inability to take oral medication, uncontrollable nausea or vomiting, history of large-scale gastrointestinal resection, uncured recurrent diarrhea, or uncured gastrointestinal diseases requiring long-term use of PPI acid-suppressing drugs); 10) The subject suffers from other primary malignant tumors, except for the following cases: Cured basal cell carcinoma or squamous cell carcinoma of the skin; Cervical carcinoma in situ; Superficial bladder cancer; 11) Meet any of the following cardiac examination results: a) The resting electrocardiogram shows a prolonged QTc interval (>450ms for men and >470ms for women), and QTcF = QT / (RR^0.33); b) The resting ECG shows various clinically significant rhythm, conduction or ECG morphology abnormalities (e.g., complete left bundle branch block, third-degree atrioventricular block, second-degree atrioventricular block, and PR period >250 ms); c) The presence of any factors that increase the risk of QTc prolongation or arrhythmic events, such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death in a first-degree relative under 40 years of age, or any concomitant medication that prolongs the QT interval; d) myocardial infarction within 6 months; 12) Pleural effusion, pericardial effusion, or ascites that is not controlled or requires repeated drainage after pleural duct drainage, VEGF inhibitors, platinum-based drug infusion, etc. before enrollment (subjects whose symptoms are stable for at least one week after treatment are eligible for enrollment); 13) Pregnant or breastfeeding women; 14) Uncontrolled or active hepatitis B virus infection (HBsAg positive, HBV-DNA>1000cps / ml (or 200IU / ml) and AST or ALT>2.0×ULN), hepatitis C virus infection or HIV infection; 15) In the judgment of the investigator, there is evidence of any severe or uncontrollable systemic disease (such as active infection, severe mental or neurological disease, unstable or uncompensated respiratory, cardiovascular, liver or kidney disease, uncontrolled hypertension [i.e., hypertension that still reaches NCI CTCAE V5.0 Grade 3 after drug treatment]), and there is no need to exclude chronic diseases; 16) Subjects who, in the researcher's judgment, may not comply with the study procedures and requirements; 17) The researcher considers the patient unsuitable to participate in this study. Research drugs, dosage and method, drug batch number Maihuatinib, tablets, batch numbers 190801, 210301, 220401, strength 45 mg; Maihuatinib, tablets, batch numbers 190911, 210311, 220211, 220311, strength 60 mg; Maihuatinib simulated tablets, tablets, batch numbers 191061, 210261, 220561, simulated 45mg strength; Maihuatinib simulated tablets, tablets, batch numbers 190941, 210241, 220441, simulated 60mg strength; Gefitinib, tablets, batch numbers 181102, 191004, 200706, 201105, 201104, 211002, strength 250 mg; Gefitinib dummy tablets, tablets, batch numbers 190931, 210231, 220531, simulated 250 mg strength; The two groups were orally administered the study drug once a day. The dosage is shown in Table 1: Table 1 Dosage regimen The subjects took the study drug whole with room temperature water on an empty stomach. Dosage schedules should be kept consistent daily, achieving a 24-hour interval. If a subject misses the scheduled medication time, they may take a supplemental dose of the study drug if the time is no more than 12 hours beyond the scheduled time window. If the time is more than 12 hours beyond the scheduled time window, they may not take a supplemental dose of the study drug and should take the next dose at the next scheduled time. If the subject vomits after taking the medication, he or she should not take the study drug again and should take the next dose of the study drug at the next scheduled medication time. During this trial, if a subject experiences a Grade 3-4 adverse event or an intolerable adverse event, medication may be suspended. Once the adverse event returns to baseline or resolves, the investigator will determine whether to continue dosing. If the adverse event still fails to return to baseline or resolve after two dose suspensions, the investigator will determine whether the subject needs a dose reduction. Each drug dose adjustment must start from the next cycle. The dose of the Maihuatinib group was adjusted from 60mg to 45mg; the gefitinib group did not have a dose reduction and was treated at the same dose. During a follow-up period, the continuous discontinuation period should not exceed 10 days, and the dose cannot be reversed after a dose reduction. Duration of treatment (trial procedure) Qualified subjects will be randomly divided into two groups in a 2:1 ratio and assigned to the experimental group or the control group. They will receive the corresponding trial drug treatment according to the grouping results until disease progression, death or intolerable toxic reactions occur. For subjects in whom disease progression is observed by all central researchers, the study drug treatment must continue until the researcher confirms it in combination with the IRC results. If the researcher's results are consistent with the IRC results, the subject can be discharged from the group; if the researcher's results are inconsistent with the IRC results, the researcher and the principal investigator of the group leader unit need to discuss and make a judgment. When the researcher assesses that the subject can continue to benefit, the subject can continue to receive treatment even if the subject reaches disease progression as defined by RECIST v1.1. Subjects can receive study drug treatment until tumor progression, death, loss to follow-up, or intolerable toxicity occurs. Subjects who withdraw from study drug treatment prematurely due to reasons other than disease progression, death, or loss to follow-up will need to receive follow-up visits, including tumor assessments, every 6 weeks until disease progression. After the subject completes treatment, the researcher still needs to contact the subject, the subject's family or the subject's current treating physician by phone once every three months to obtain the subject's overall survival data until the subject's death. Table 2 Study time and treatment time of the two groups of patients (SS) Note: Study duration (days) = (study end date - informed consent date) + 1 (subjects completing the study) Study time (days) = (exit date - informed consent date) + 1 (subject withdraws early). If the exit date is missing, the death date is used as the exit date for calculation. Treatment time (days) = (last medication date - first medication date) + 1 (trial period) Total dose (tablets) = the sum of the doses recorded in the medication record Compliance (%) = actual total dose taken / theoretical total dose taken × 100%. Evaluation Criteria Efficacy evaluation Primary endpoint: Progression-free survival (PFS) was assessed by an independent review committee (IRC) according to the RECIST v1.1 criteria. PFS was defined as the time (in months) from the date of treatment to the first observation of disease progression (based on imaging). For subjects who died of other causes before disease progression, the time (in months) from the date of treatment to death was calculated. Secondary endpoints: Overall survival (OS) was assessed by the investigator; OS was defined as the time from randomization to death due to any cause (the last follow-up date for subjects lost to follow-up and the end of follow-up date for subjects still alive at the end of the study). Progression-free survival (PFS), investigator-assessed. The objective response rate (ORR) was assessed by both the IRC and the investigator. ORR refers to the proportion of patients whose tumors achieve and maintain a certain duration of reduction, including both complete response (CR) and partial response (PR). Objective response was determined using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Subjects must have measurable tumor lesions at baseline and be selected as target lesions. The duration of response (DoR) was assessed by IRC and investigators respectively; DoR was defined as the time from the first tumor assessment as CR or PR to the first assessment as PD or death from any cause. Disease control rate (DCR) was assessed by IRC and investigators respectively; DCR was defined as the percentage of confirmed complete remission, partial remission, and stable disease (≥8 weeks) among subjects who could be evaluated for efficacy. Time to progression (TTP) was assessed by the IRC and investigators, respectively; TTP was defined as the time from the date of treatment to tumor progression, excluding data from deceased subjects. Disease control rate (DCR) was assessed by IRC and investigators respectively; DCR was defined as the percentage of confirmed complete remission, partial remission, and stable disease (≥8 weeks) among subjects who could be evaluated for efficacy. Time to progression (TTP) was assessed by the IRC and investigators, respectively; TTP was defined as the time from the date of treatment to tumor progression, excluding data from deceased subjects. Time to Failure (TTF): TTF is a composite endpoint, which is the time from randomization to withdrawal from treatment for any reason (including disease progression, treatment toxicity, and death). Other endpoints: Health-related quality of life (HRQoL) was assessed using the European Organization for Research and Treatment (EORTC) QLQ-C30 and QLQ-LC13. Evaluation methods: Changes in relevant clinical symptoms and objective examination results were observed before and after treatment and scored. Scores for each domain of the scale were recorded in the electronic case report form as required. Effectiveness results Primary endpoint: IRC-assessed PFS: *a The percentage is calculated using the following method: n / N*100%; *E hazard ratio (HR) (experimental group vs control group) was calculated using the Cox regression method with censored data. In the FAS, there were 166 events (74.4%) in the experimental group, with 57 (25.6%) censored cases; there were 96 events (85.0%) in the control group, with 17 (15.0%) censored cases. The median PFS in the experimental group was 13.730 (95% CI: 11.040, 15.180) months vs 9.660 (95% CI: 8.340, 12.390) months in the control group. The hazard ratio between the two groups was 0.68 (95% CI: 0.53, 0.87). The stratified log-rank test showed a statistically significant difference in PFS between the two groups (χ 2 =9.20, P = 0.0024), and the unstratified log-rank test as a supporting analysis was consistent with the primary analysis results (HR = 0.69; 95% CI: 0.54, 0.89; P = 0.0040). Secondary endpoints: Investigator-assessed PFS: According to investigator assessment, the number of events in the FAS was 170 (76.2%) in the experimental group and 101 (89.4%) in the control group. The median PFS in the experimental group was 13.730 months, superior to 9.720 months in the control group (HR: 0.70; 95% CI: 0.55, 0.90; P = 0.0042). The PPS results were similar to those in the FAS, consistent with the primary endpoint. OS: In the FAS, the number of events in the experimental group and the control group was 83 (37.2%) and 45 (39.8%), respectively. The median OS after treatment was 35.420 months in the experimental group and 33.310 months in the control group, respectively, with no statistically significant difference between the two groups (HR: 0.90; 95% CI: 0.63, 1.30; P = 0.5768). The 30-month OS rates were 60.2% (95% CI: 52.5%, 67.1%) and 54.3% (95% CI: 41.9%, 65.1%), respectively. The PPS results were consistent with the FAS. ORR: According to IRC assessment, in the FAS, 1 patient in the experimental group achieved a complete remission (CR), 180 patients achieved a partial remission (PR), 19 patients developed symptomatic disease (SD), 12 patients developed progressive disease (PD), and 11 patients developed no progressive disease (NED). In the control group, 1 patient achieved a complete remission (CR), 87 patients achieved a partial remission (PR), 14 patients developed symptomatic disease (SD), 2 patients developed progressive disease (PD), and 9 patients developed no progressive disease (NED). The ORR in the experimental and control groups was 81.2% (95% CI: 75.4%, 86.1%) and 77.9% (95% CI: 69.1%, 85.1%), respectively, with no statistically significant difference between the two groups (P = 0.4772). The OR between the two groups was 1.23 (95% CI: 0.70, 2.14). The PPS results were consistent with the FAS results. According to investigator assessment, in the FAS, 160 patients in the experimental group had a PR, 42 had SD, 12 had PD, 9 had NE, and no CR; in the control group, 66 had a PR, 33 had SD, 7 had PD, 7 had NE, and no CR. The ORR in the experimental and control groups was 71.7% (95% CI: 65.4%, 77.6%) and 58.4% (95% CI: 48.8%, 67.6%), respectively, a statistically significant difference between the two groups (P = 0.0139). The OR between the two groups was 1.81 (95% CI: 1.12, 2.90). The PPS results were consistent with the FAS. DCR: According to IRC assessment, in the FAS, the DCR in the experimental group and the control group were 89.7% (95% CI: 84.9%, 93.3%) and 90.3% (95% CI: 83.2%, 95.0%), respectively, with no statistically significant difference between the two groups (P = 0.8679). The OR between the two groups was 0.94 (95% CI: 0.44, 1.99). The PPS results were consistent with the FAS. According to the investigators' assessment, the DCR in the experimental group and the control group on the FAS was 90.6% (95% CI: 86.0%, 94.1%) vs 87.6% (95% CI: 80.1%, 93.1%), respectively. The difference between the two groups was not statistically significant (P = 0.4004). The OR between the two groups was 1.36 (95% CI: 0.66, 2.79). The PPS results were consistent with the FAS. The investigators' assessment of the DCR results was consistent with the IRC assessment. DoR: According to IRC assessment, the FAS showed that the number of events in the experimental group and the control group was 136 (75.1%) and 76 (86.4%), respectively. The experimental group had a significantly longer DoR (12.550 months) compared with the control group (9.690 months), with a between-group difference (HR = 0.68; 95% CI: 0.52, 0.91; P = 0.0076). The PPS results were similar to those of the FAS. According to investigator assessment, the FAS showed that the number of events in the experimental group (76.3%) and the control group (89.4%) was 122 (95% CI: 0.58, 1.09) and 59 (95% CI: 89.4) respectively. The median duration of response (DOR) was 12.520 months in the experimental group and 11.470 months in the control group, respectively. There was no statistically significant difference between the two groups (HR = 0.80; 95% CI: 0.58, 1.09; P = 0.1528). The PPS results were similar to those in the FAS. TTF: The number of events in the experimental group and the control group was 180 (80.7%) and 103 (91.2%), respectively. The experimental group was able to delay TTF (12.910 months) compared with the control group (11.500 months), with a statistically significant difference between the two groups (HR = 0.76; 95% CI: 0.60, 0.97; P = 0.0255). The PPS results were consistent with the FAS. TTP: According to IRC assessment, the number of events in the FAS was 159 (71.3%) in the experimental group and 91 (80.5%) in the control group. The experimental group was able to delay TTP (13.800 months) compared with the control group (9.690 months), with a statistically significant difference between the two groups (HR = 0.70; 95% CI: 0.54, 0.90; P = 0.0054). The PPS results were similar to those of the FAS. The researchers assessed that in the FAS, the number of events in the experimental group and the control group was 163 (73.1%) and 95 (84.1%), respectively. The experimental group was able to delay TTP (13.800 months) compared with the control group (11.140 months), with a statistically significant difference between the two groups (HR = 0.72; 95% CI: 0.56, 0.93; P = 0.0108). The PPS results were similar to those of the FAS. HRQoL: In the EORTC QLQ-C30 score, there were statistically significant differences in appetite loss and diarrhea between the experimental group and the control group at week 24 (V8) after treatment (P < 0.05). There was also a statistically significant difference in the change in diarrhea compared with the baseline between the two groups (P < 0.05). The FAS results were consistent with the PPS results. In the QLQ-LC13 scores, there were statistically significant differences in oral pain and tingling in the hands and feet between the experimental group and the control group at week 24 (V8) after treatment (P < 0.05), and the changes compared with the baseline were also statistically significant (P < 0.05). The FAS results were consistent with the PPS results. Discussion and overall conclusions discuss The first-generation EGFR-TKIs gefitinib, erlotinib, and icotinib were approved in China in 2011, 2017, and 2014, respectively, for the first-line treatment of advanced EGFRm+NSCLC. These drugs were approved in key registrational clinical trials for the first-line treatment of advanced EGFRm+NSCLC compared with platinum-based doublet chemotherapy due to their superior mPFS compared with chemotherapy. The second-generation EGFR-TKI afatinib was also approved in 2017 for its mPFS advantage compared with platinum-based doublet chemotherapy for the first-line treatment of advanced EGFRm+NSCLC. However, no mOS benefit was observed for these drugs in the first-line treatment of advanced EGFRm+NSCLC compared with platinum-based doublet chemotherapy for the first-line treatment of advanced EGFRm+NSCLC [1][2][3][5]. The second-generation EGFR-TKI dacomitinib and the third-generation EGFR-TKIs osimertinib, ametinib, and vumetinib were all evaluated in pivotal registrational clinical trials as first-line treatment for advanced EGFRm+ NSCLC, compared to the first-generation EGFR-TKI gefitinib. These drugs were approved in 2019, 2019, 2021, and 2022, respectively, based on their mPFS advantages over gefitinib. The third-generation EGFR-TKI osimertinib demonstrated slightly inferior mPFS in patients with the EGFR L858R mutation (14.4 months vs. 9.4 months) compared to those with the EGFR 19del mutation (21.4 months vs. 11 months). In the overall population, osimertinib demonstrated a mOS advantage over gefitinib (38.6 months vs. 31.8 months), but no mOS advantage was observed for first-line osimertinib compared with gefitinib in patients with the EGFR L858R mutation (HR = 1.0). The third-generation EGFR-TKIs ametinib, vumetinib, and befortinib were also observed to have slightly worse mPFS in patients with EGFR L858R mutations than in patients with EGFR 19del mutations, and the mOS data are not yet mature [6]-

[0015] Dacomitinib showed a significant mPFS advantage in patients with both EGFR 19del mutations and EGFR L858R mutations, and a mOS advantage in the overall population and patients with EGFR L858R mutations (37.7 months vs 29.1 months in the overall population; 32.5 months vs 23.2 months in EGFR L858R). [8] In subsequent real-world studies, afatinib or gefitinib was used as first-line treatment followed by osimertinib, and the PFS of first- / second-generation EGFR-TKIs followed by osimertinib was comparable to that of first-line osimertinib. In addition, the OS of patients treated with first- / second-generation EGFR-TKIs as first-line treatment was comparable to that of patients treated with osimertinib as first-line treatment.

[0016]

[0017] As first-line treatment, afatinib followed by osimertinib showed a trend of better PFS and OS than osimertinib in patients with EGFR L858R mutation and those without brain metastases.

[0016] . The currently approved second-generation EGFR-TKIs are less well tolerated in clinical use than the first- and third-generation EGFR-TKIs. In a clinical study of afatinib versus gefitinib, 42% of patients in the afatinib group required dose reduction (compared to 2% of patients in the gefitinib group).

[0018] In the dacomitinib versus gefitinib clinical study, 66% of patients in the dacomitinib group required dose reductions (compared to 8% of patients in the gefitinib group). [8] In clinical studies comparing third-generation EGFR-TKIs with gefitinib, the proportion of patients requiring dose reduction was comparable to that of the first-generation EGFR-TKI control group.

[0011]

[0019]

[0020] Only a higher proportion of patients required dose reduction for befortinib

[0015] After treatment with second-generation EGFR-TKIs, secondary T790M mutations remain the primary resistance mechanism. (Source not found.) Better-tolerated first-line drugs can allow patients to benefit more from second- to third-generation sequential therapy. In summary, patients with EGFRm+NSCLC can choose third-generation EGFR-TKIs as first-line treatment in the advanced stage, or they can choose third-generation EGFR-TKIs if EGFR T790M mutation appears after progression of first- or second-generation EGFR-TKIs. For some populations, such as patients with EGFR L858R mutation or patients without brain metastases, there is evidence to support that second-generation drugs as first-line treatment can bring better patient benefits. Among the second-generation EGFR-TKIs currently approved in China, only dacomitinib has shown efficacy advantages over the first-generation EGFR-TKI gefitinib, and its advantage over gefitinib in the L858R population still has room for improvement (dacomitinib HR = 0.63 [8] , osimertinib HR = 0.51

[0010] , ametinib HR = 0.60

[0012] , vometinib HR = 0.54

[0014] , befortinib HR = 0.63

[0015] The currently approved second-generation EGFR-TKIs have suboptimal tolerability, primarily due to the need for dose adjustments in a large number of patients. Maihuatinib tablets are a novel, irreversible EGFR / HER2 inhibitor. Preclinical studies have shown that they effectively inhibit wild-type and mutant EGFR and HER2 signaling pathways. Completed Phase II study results demonstrate that Maihuatinib tablets are safe and effective as first-line treatment for advanced NSCLC harboring EGFR-sensitive mutations. The 60mg and 80mg doses demonstrated comparable efficacy, with the 60mg dose providing superior safety compared to the 80mg dose. This study has reached the primary endpoint (PFS) with statistically significant improvement. Compared with gefitinib (9.660 months), mehuatinib treatment can prolong PFS (13.730 months), reduce risk by 32%, and benefit is observed in various pre-specified subgroups of gender, age, smoking history, mutation type, and ECOG score. In patients with L858R mutations, mehuatinib has superior efficacy compared with gefitinib (primary study endpoint PFS HR = 0.55), and is equivalent to or better than approved second-generation or third-generation EGFR-TKIs (dacomitinib HR = 0.63). [8] , osimertinib HR = 0.51

[0011] , ametinib HR = 0.60

[0013] , vometinib HR = 0.54

[0014] , befortinib HR = 0.63

[0015] ). The AE characteristics of Maihuatinib in this study were consistent with previous clinical trial experience, and no new safety issues were found. The proportion of patients who experienced dose reductions with Maihuatinib was comparable to that with gefitinib, and significantly lower than that with currently approved second-generation EGFR-TKIs. [8]

[0018] The low incidence of adverse events leading to permanent discontinuation and dose reductions suggests that the recommended dosing and dose modification schedule can make patients tolerate mavartinib treatment well. Overall conclusion Maihuatinib tablets are safe and effective as first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC) harboring EGFR-sensitive mutations. In the control group of this study, the median PFS for patients with EGFR-mutant NSCLC treated with gefitinib, a first-line treatment, was 9.660 months, similar to the results of the IPASS study. Maihuatinib, with a median PFS of 13.730 months, was significantly superior to gefitinib. In patients with the L858R mutation, Maihuatinib showed a trend toward superiority over approved second-generation EGFR-TKIs and exhibited good long-term tolerability, with a significantly lower rate of dose reductions than currently approved second-generation EGFR-TKIs. Maihuatinib may benefit patients as a superior first-line second-generation EGFR-TKI. Example 2 Second Generation Genome Testing Based on the patients enrolled in Example 1, samples that failed quality control were excluded, and EGFR-related gene sequencing was performed on 288 tumor sections (189 in the mahuatinib group and 99 in the gefitinib group). Test information: From Adicon Medical Testing Company https: / / alms-dev.adicon.com.cn Detection gene list ABL1 AKT2 AKT3 ARAF AXIN1 BCR BTK CDC73 CSF1R CTNNB1 CYP2B6 CYP2C19 CYP2C9 CYP2D6 CYP3A4 DDR2 DPYD EIF1AX ERBB3 ERBB4 ERCC2 EZH2 FLT3 FLT4GATA3 GNA11 GNAQ GNAS HNF1A HOXB13 IDH1 IDH2 JAK1 JAK3 KDM6A KDR MAP2K1 MAP2K2 MPL MTHFR MTOR MYD88 NFE2L2 NOTCH1 NPM1 PDGFRB PIK3R1 PPP2R1A PTCH1 RAC1 RAF1 RHOA RIT1 RNF43 SF3B1 SRC TERT TPMT TSHR U2AF1 UGT1A1 VKORC1 AKT1 ALK APC AR ARID1A ATM BRAF BRCA1 BRCA2 BRIP1 CCND1 CCND2 CCND3 CCNE1 CD274 CDH1 CDK12 CDK4 CDK6 CDKN2A CDKN2B CHEK2 EGFR EPCAM ERBB2 ESR1 FANCA FBXW7 FGF19 FGFR1 FGFR2 FGFR3 FGFR4 FOXL2 GEN1 HRAS JAK2 KEAP1 KIT KRAS MDM2 MET MLH1 MSH2 MSH6 MUTYH MYC MYCN NBN NF1 NF2 NRAS NTRK1 NTRK2 NTRK3 PALB2 PDCD1LG2 PDGFRA PIK3CA PMS2 POLE PTEN PTPN11 RAD51C RAD51D RB1 ROS1 SMAD4 SMARCB1 SMO STK11 TP53 TSC1 TSC2 VEGFA VHL ALK BRAF CD74 EGFR ETV6 EWSR1 FGFR1 FGFR2 FGFR3 JAK2 MET NTRK1 NTRK2 PAX8 PDGFRA PDGFRB RAF1 RET ROS1 SDC4 SLC34A2 SLC3A2 THADA TMPRSS2 VAMP2 NRG1 NTRK3 BAT-RII BAT25 EWSR1 MSIPlus_01 MSIPlus_03 MSIPlus_06 MSIPlus_08MSIPlus_13MSIPlus_14 NR21 NR22 NR27 BRCA1 CDKN2B MLH1 TERT Next-generation genome sequencing results Of the 288 available tumor samples, 201 samples were found to harbor deleterious mutations and were included in the biomarker study. The test results are shown in Table 3. Table 3 Of the 288 available tumor samples (189 / 99 in the mahuatinib group and 67 in the gefitinib group), 201 samples (134 in the mahuatinib group and 67 in the gefitinib group) showed deleterious mutations. Among the patients aged 36 to 75 years, 128 had both EGFR and TP53 mutations, accounting for 63.7% of the samples with detected mutations. Example 3 Statistical Analysis Determination of sample size: The purpose of this study was to explore the effects of the experimental drug mahuatinib and the control drug gefitinib in different gene co-mutation populations. The analysis population was entirely from the Phase III clinical trial in Example 1, so no formal statistical assumptions or sample size calculations were made in this study. The sample size for the Phase III clinical trial in Example 1 was calculated as follows: This study is a randomized, parallel-controlled, double-blind, double-dummy, multicenter, superior-efficacy Phase III clinical study. According to the "Technical Guidelines for Endpoints in Clinical Trials of Advanced Non-Small Cell Lung Cancer (Draft for Comment)" issued in June 2019, PFS is used instead of OS as the efficacy endpoint, and "a 4-month PFS benefit in non-squamous cell carcinoma has significant clinical value, and the target HR point estimate is generally no higher than 0.70." Assuming a PFS hazard ratio (HR) of 0.69 for mevatinib versus gefitinib (median PFS 10 months in the gefitinib group and 14.5 months in the mevatinib group), a trial with a ratio of 2:1 for control, an enrollment period of 12 months, a study duration of 36 months, a one-sided α of 0.025, and a power of 80%, 256 events were needed to detect a statistical difference in PFS between the groups. Based on a 10% loss to follow-up rate, approximately 336 subjects would need to be enrolled. Analyze the dataset: All patients (288) who were enrolled in the Phase III study, took at least one trial drug, and had at least one NGS test result in Example 1 were analyzed. Treatment groups were analyzed according to randomization. Analytical methods: The distribution of each mutation in different populations will be presented as frequency and percentage. Percentages will be presented to one decimal place. Intergroup differences in survival endpoints (progression-free survival (PFS)—assessed by IRC—and overall survival (OS)) will be compared across different mutation subgroups in different populations. Intergroup comparisons will be performed using the log-rank test, and the Cox proportional hazards model will be used to estimate hazard ratios (HRs) and their 95% confidence intervals (CIs). The 95% CIs for the HRs will be calculated using the Wald method. The Kaplan-Meier method will be used to estimate median PFS and OS, along with their 95% CIs, and Kaplan-Meier curves will be plotted. Exploratory analyses will be conducted for the following populations and groups: For PFS indicators: Comparisons across all populations: Maihuatinib group & EGFR mutation combined with deleterious mutations vs. gefitinib group & EGFR mutation combined with deleterious mutations Maihuatinib group & EGFR mutation combined with deleterious TP53 mutation vs. gefitinib group & EGFR mutation combined with deleterious TP53 mutation Maihuatinib group & EGFR 19del Combined deleterious mutations vs. gefitinib group & EGFR 19del Combined deleterious mutations Maihuatinib group & EGFR 19delCombined deleterious TP53 mutation vs. gefitinib group & EGFR 19del Combined deleterious TP53 mutations Maihuatinib group & EGFR L858R Combined deleterious mutations vs. gefitinib group & EGFR L858R Combined deleterious mutations Maihuatinib group & EGFR L858R Combined deleterious TP53 mutation vs. gefitinib group & EGFR L858R Combined deleterious TP53 mutations For OS metrics: Comparisons across all populations: Maihuatinib group & EGFR mutation combined with deleterious mutations vs. gefitinib group & EGFR mutation combined with deleterious mutations Maihuatinib group & EGFR mutation combined with deleterious TP53 mutation vs. gefitinib group & EGFR mutation combined with deleterious TP53 mutation Maihuatinib group & EGFR 19del Combined deleterious mutations vs. gefitinib group & EGFR 19del Combined deleterious mutations Maihuatinib group & EGFR 19del Combined deleterious TP53 mutation vs. gefitinib group & EGFR 19del Combined deleterious TP53 mutations Maihuatinib group & EGFR L858R Combined deleterious mutations vs. gefitinib group & EGFR L858R Combined deleterious mutations Maihuatinib group & EGFR L858R Combined deleterious TP53 mutation vs. gefitinib group & EGFR L858R Combined deleterious TP53 mutations All hypothesis tests were two-sided, with an α of 0.05. Differences were considered statistically significant if the two-sided P value was ≤ 0.05. All confidence intervals were two-sided with a confidence level of 95%. Based on the above mutations and the patients' disease progression, the statistical analysis results are as follows Table 4-Table 5 Table 4 Analysis of the above gene test results and corresponding subjects' PFS (months) - FAS Table 5 OS analysis by deleterious mutation classification - FAS in conclusion In patients with advanced non-small cell lung cancer with EGFR mutations and deleterious mutations, mahuatinib was associated with a significantly improved PFS compared with gefitinib: in the overall population (mPFS: 12.550 months vs 9.56 months, HR=0.56, P=0.0005), EGFR 19del Combined deleterious mutations (mPFS: 12.550 months vs 12.39 months, HR=0.65, P=0.0753), EGFR L858R Combined deleterious mutations (mPFS: 13.70 months vs 8.28 months, HR = 0.44, P = 0.0004); OS: in the overall population (HR = 0.54, P = 0.0045), EGFR 19del Combined deleterious mutations (HR=0.75, P=0.4121), EGFR L858R Combined with deleterious mutations (HR=0.40, P=0.0006), mahuatinib showed significant advantages over gefitinib in terms of PFS and OS. In EGFR L858R In patients with combined deleterious mutations, the HR advantage of Maihuatinib over Gefitinib in PFS exceeded the previously reported HR advantage of EGFR-TKIs over Gefitinib. L858R In the population with combined deleterious mutations, the HR advantage of mahuatinib over gefitinib in OS exceeded the previously reported HR advantage of EGFR-TKIs over gefitinib. Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present application, rather than to limit them. Although the present application has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present application. References [1]. Fukuoka M, Wu YL, Thongprasert S, et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin / paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS)[J]. J Clin Oncol. 2011;29(21):2866-74. [2]. Wu YL, Zhou C, Liam CK, et al. First-line erlotinib versus gemcitabine / cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study[J]. Ann Oncol. 2015;26(9):1883-1889. [3]. Betta Pharmaceutical Co., Ltd., Instruction Manual of Icotinib Hydrochloride Tablets, 2017. [4]. Shi YK, Wang L, Han BH, et al. 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