| Background and objectiveLung cancer is the malignant tumor with the highest morbidity and mortality worldwide.So far,the morbidity and mortality of lung cancer patients in our country are increasing day by day.It is very important to explore effective treatment options to prolong the survival time of patients with advanced lung cancer.The histological types of lung cancer include non-small cell lung cancer and small cell lung cancer.Among them,non-small cell lung cancer is the most common type,accounting for about 85%of all types.SCLC is sensitive to radiotherapy and chemotherapy,but it is easy to relapse and metastasize.In comparison,the disease progression of NSCLC patients is slower.Non-small cell lung cancer includes lung adenocarcinoma,lung squamous cell carcinoma,and large cell carcinoma,among which the more common type is lung adenocarcinoma.In NSCLC patients,especially those with lung adenocarcinoma,most of them are accompanied by driver gene mutations.Among them,epidermal growth factor receptor gene mutations are more common.Among all populations,lung adenocarcinomas in women who have never smoked are most likely to develop EGFR mutations.Among EGFR gene mutations,the most common types are the 19 exon deletion mutation and the 21 exon L858R point mutation,accounting for 80%-90%of all mutations,which are called sensitive mutations.In addition,EGFR gene mutations also include exon 18 G719X mutation,exon 20 insertion mutation and exon 20 T790M resistance mutation,which are collectively referred to as rare mutations.At present,a number of preclinical and clinical studies have been carried out on the treatment of sensitive mutations in the EGFR gene,which has deepened our understanding of the molecular mechanism of sensitive mutations and the therapeutic efficacy.For advanced non-small cell lung cancer patients with classic mutations,the first-line treatment with tyrosine kinase inhibitors can significantly prolong the patient’s progression-free survival and overall survival time.However,the understanding of the insertion mutation of EGFR gene 20 is not enough,and the research of effective targeted drugs for it has not made significant progress.This study analyzed the clinical characteristics and efficacy of NSCLC patients with 20 insertion mutations to provide a basis for the selection of clinical treatment options for patients with 20 insertion mutations in the EGFR gene.MethodsA continuous collection of 267 patients who were pathologically diagnosed with non-small cell lung cancer in the First Affiliated Hospital of Zhengzhou University from January 2011 to December 2020 and genetically detected an insertion mutation in exon 20 of the EGFR gene.Collecting the clinical characteristics of patients based on outpatient records and case information,including age,gender,tissue type,TNM stage,whether there is a history of smoking,whether there is brain metastasis at the first visit and so on.And comprehensively analysing the clinical characteristics of patients with EGFR gene 20 exon insertion mutations.According to the inclusion and exclusion criteria,a total of 54 untreated patients with advanced lung adenocarcinoma met the enrollment requirements,and 13 patients were treated with EGFR-TKIs as the first-line treatment,that is,the targeted therapy group.27 patients were treated with standard platinum-containing dual-drug therapy,namely chemotherapy alone group,and 14 patients were treated with chemotherapy combined with bevacizumab as the first-line treatment,namely the combined treatment group.Patients in the targeted therapy group were rechecked with CT after taking the drug for at least 30 days.The chemotherapy alone group and the targeted therapy group were rechecked with CT every 2 cycles,and the efficacy was evaluated according to the RECIST 1.1 standard.The endpoint of this study is the progression free survival of the disease.PFS is defined as the first treatment after the diagnosis of the patient to the first progression of the disease or death due to any reason.The SPSS 21.0 system was used for statistical analysis.The survival curve was drawn by Kaplan-Meier,and the PFS between each group was compared by log-rank test.Two-sided P values<0.05 were defined as statistically different.Results1.Clinical characteristics:in the 267 patients,overall male patients(47.6%)are more than female patients(52.4%);patients less than 60 years old(53.9%)are more than patients ≥60 years old(46.1%);The number of patients with no previous smoking history(74.2%)was more than that of patients with previous smoking history(25.8%);the tissue type was lung adenocarcinoma patients(97.8%)more than non-adenocarcinoma patients(2.2%);There were more patients at TNM stage Ⅲ-Ⅳ(67.8%)than patients at stage Ⅰ-Ⅱ(32.2%);the number of patients without brain metastases at the first diagnosis(82.4%)was more than the patients diagnosed with brain metastases(17.6%).The 54 patients included in the clinical analysis were all lung adenocarcinomas,28 were male patients(51.9%),26 were female patients(48.1%);32 patients(59.3%)were younger than 60 years old,and 22 patients were older than 60 years old(40.7%);40 patients(74.1%)with no previous smoking history,14 patients(25.9%)with previous smoking history;7 patients(13.0%)with TNM stage Ⅲ and 47 patients with stage Ⅳ(87.0%);14 cases(25.9%)were diagnosed with brain metastases at the first diagnosis,and 40 cases(74.1%)were not accompanied by brain metastases.Under subgroup analysis,the most common mutation subtype among the 267 patients and 54 patients included in the clinical analysis was p.D770_N771insG,which was 118(44.2%)and 25(46.3%)respectively.There were only 2 patients with A763_Y764insFQEA mutation subtype,accounting for 0.7%of all 20 exon insertion mutations.2 patients(100%)were male patients;1 patient(50%)aged less than 60 years old,1 patient(50%)aged 60 years or older;1 patient(50%)without a history of smoking,had a previous smoker 1 patient with history(50%);2 patients had lung adenocarcinoma(100%);2 patients(100%)had TNM stage Ⅳ;2 patients(100%)were not at first diagnosis with brain metastases.2.Efficacy analysis:the median PFS of patients in the targeted therapy group was 2.57 months,the median PFS of patients in the chemotherapy alone group was 5.37 months,and the median PFS of patients in the combined therapy group was as high as 12.57 months(P<0.001).A pairwise comparison of the three groups of treatment programs found that the difference in survival curves between each two groups was statistically significant(P<0.01).Subgroup analysis of mutation subtypes:In the targeted therapy group,1 patient with A763_Y764insFQEA mutation received the first-generation EGFR-TKI(icotinib)treatment with a PFS of 5.67 months.in the combined treatment group,there was 1 patient of A763_Y764insFQEA mutation having a PFS of 6.60 months.Analysis of the subgroups of the combined treatment group:①group median PFS was 4.67 months,②group median PFS was 12.57 months and③group median PFS was 9.30 months.None of the 3 maintenance treatment options have statistical difference(P=0.127).3.Analysis of factors affecting patients’ PFS:in the targeted therapy group and chemotherapy alone group,age,gender,smoking,whether there was brain metastasis at the first diagnosis,and TNM stage were not significantly correlated with patients’PFS(P>0.05).In the combined treatment group,age was significantly correlated with patients’ PFS(P=0.046),while factors such as gender,smoking,whether there were brain metastases,and TNM staging were not significantly correlated with patients’ PFS(P>0.05).Conclusions1.Among the NSCLC population with insertion mutation in exon 20 of the EGFR gene,women with advanced lung adenocarcinoma who are younger than 60 years old and have no previous smoking history are more common.While in the patients with the subtype A763_Y764insFQEA sensitive mutation,male Patients with advanced lung adenocarcinoma without brain metastasis are more common.2.For NSCLC patients with EGFR gene 20 exon insertion mutation,the platinum-containing dual-agent chemotherapy combined with bevacizumab is better than platinum-containing dual-agent chemotherapy as a first-line treatment,while patients is almost impossible benefiting from the first-generation EGFR-TKIs single-agent treatment.However,the A763_Y764insFQEA mutation as the only sensitive mutation in exon 20 may benefit from single-agent EGFR-TKIs treatment.3.In the targeted therapy group and the chemotherapy alone group,age,gender,smoking,whether there was brain metastasis at the first diagnosis,and TNM stage were not significantly correlated with the PFS of the patients(P>0.05).In the combined treatment group,age was significantly correlated with patients’ PFS(P=0.046),while factors such as gender,smoking,whether there were brain metastases,and TNM stage were not significantly correlated with patients’ PFS(P>0.05).That is,younger patients are more likely to benefit from platinum-containing dual-drug chemotherapy combined with bevacizumab therapy than older patients. |
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