Comparative Study Of First-Line Treatment Regimens For EGFR Rare Mutation-Positive Advanced Non-Small Cell Lung Cancer

Objectives:The aim of this study is to investigate the efficacy and safety of different first-line treatment regimens in patients with advanced non-small cell lung cancer(NSCLC)who harbor rare mutations in the epidermal growth factor receptor(EGFR).Methods:This study collected genetic testing reports,clinical characteristics data,and treatment process information of 186 patients with advanced non-small cell lung cancer(NSCLC)from Yunnan Cancer Hospital between January 1,2017 and December 31,2021.These patients were confirmed to harbor rare mutations in the epidermal growth factor receptor(EGFR),including both single and complex EGFR mutations.According to different first-line treatment regimens,patients were divided into three groups: targeted monotherapy group(n=137),chemotherapy group(n=24),and targeted combined chemotherapy group(n=25).The study evaluated patients’ objective response rate(ORR)and disease control rate(DCR)under first-line treatment according to RECIST 1.1 criteria,while using CTCAE 5.0 criteria to assess adverse reactions.Statistical analysis was performed using SPSS 25.0 software,and the chi-square test was used to verify whether the distribution of clinical characteristics among groups was homogeneous.The Kaplan-Meier method was used to calculate progression-free survival(PFS)for different groups and to conduct univariate survival analysis.The Cox proportional hazards model was used to perform multivariate survival analysis to identify independent factors affecting first-line PFS in patients with EGFR rare mutations.Differences with a two-sided P-value less than0.05 were considered statistically significant.Results: After organizing and analyzing the collected data,we found that:1.Among the collected cases of advanced NSCLC in this study,patients with EGFR rare mutations had a higher proportion in those under the age of 60,with no smoking history,and with adenocarcinoma.Among them,EGFR compound mutations accounted for 78.5% and were the most common type of rare mutations.2.Patients were divided into three groups based on different first-line treatment regimens,with balanced distribution of clinical characteristics.Among them,the majority of patients(137 cases,73.3%)received targeted monotherapy as the first-line treatment,24 cases(12.9%)received chemotherapy,and 25 cases(13.4%)received targeted combined with chemotherapy.After pairwise comparison of PFS among the three groups by Log-Rank test,it was found that the PFS of the chemotherapy group was significantly lower than that of the targeted monotherapy group and the targeted combined with chemotherapy group(P=0.009).The median PFS of the targeted combined with chemotherapy group was longer than that of the targeted monotherapy group,but the difference was not statistically significant(12.3 vs.10.03 months,P=0.894).3.Using the COX proportional hazards model,we conducted a multivariate analysis of factors that may affect PFS in patients with EGFR rare mutations in advanced NSCLC.The results showed that treatment strategy was an independent factor affecting PFS.Targeted monotherapy and targeted combination chemotherapy as first-line treatment for patients with EGFR rare mutations in advanced NSCLC can reduce the risk of progression.4.After statistical analysis of treatment-related adverse reactions in the three groups of patients,it was found that the incidence of adverse reactions in the targeted combined chemotherapy group was generally higher,but overall safe and did not increase the incidence of grade III or higher adverse events.5.Further analysis of patients in the targeted monotherapy group showed that the use of second/third-generation EGFR-TKIs compared to first-generation EGFR-TKIs resulted in a longer median PFS(11.20 vs 9.10 months,P=0.304),especially for patients carrying a single rare EGFR mutation,where the first-line use of second/third-generation EGFR-TKIs was significantly beneficial compared to first-generation EGFR-TKIs(median PFS: 16.87 vs 7.47 months,P=0.009).Conclusions:1.For advanced NSCLC patients with EGFR rare mutations,the first-line efficacy is related to treatment regimens and mutation types.In the real world,most of these patients choose EGFR-TKIs as first-line targeted monotherapy,and first-line targeted monotherapy or targeted combined chemotherapy can achieve longer PFS benefits compared to monotherapy chemotherapy,with controllable safety.2.For advanced NSCLC patients with EGFR rare single mutations(G719X,L861 Q,or S768I),first-line treatment with second-generation or third-generation EGFR-TKIs targeted monotherapy is recommended.3.Less common mutations in the epidermal growth factor receptor(EGFR)occur in advanced non-small cell lung cancer(NSCLC),with compound mutations being more common.