Efficacy And Toxicity Analysis Of Immunotherapy For EGFR-positive Non-small Cell Lung Cancer Patients After Resistance To Targeted Drugs

Objective: The treatment of malignant tumors has entered the era of molecular targeted therapy and immunotherapy.For EGFR-mutated advanced non-small cell lung cancer,the current standard treatment is based on molecular targeted drugs.With targeted drugs,the duration of disease control can be greatly extended and a better quality of survival can be achieved.The biggest hurdle to targeted therapy is the inevitable emergence of drug resistance,and treatment options and therapeutic effect are very limited after the progression of drug resistance,making it one of the current clinical treatment challenges.With the increasing maturity of immunotherapy,the application of immune checkpoint inhibitors for anti-tumor therapy has significantly improved the efficacy of most malignant tumors.However,the clinical application of immunotherapy after targeted drugs resistance in such patients is relatively rare,and the efficacy and safety are uncertain.In order to observe the actual situation in the real-world,this study retrospectively analyzed the efficacy and toxicity of immune combination therapy in advanced NSCLC patients with EGFR sensitizing mutations after drug resistance,and proposed a possible beneficiary population to provide clinical data and information for the precise treatment of advanced NSCLC patients with an EGFR sensitizing mutation after targeted drugs resistance.Methods: Information on patients with advanced NSCLC with EGFR sensitizing mutations admitted to Sichuan Cancer Hospital between January 2019 and June 2020 were collected according to inclusion and exclusion criteria,including age,gender,smoking status,previous treatment status,cause of gene mutation and resistance,treatment regimen after drug resistance,and adverse reactions to treatment,etc.All patients were treated with PD-1 inhibitors combined with chemotherapy or antiangiogenic drugs after progression of resistance to targeted therapy.The research focuses on their progression free survival,overall survival,objective response rate and common immune-related adverse events for preliminary observation and analysis.Results: 32 cases of advanced NSCLC patients treated at Sichuan Cancer Hospital were collected.The EGFR gene mutation types in all cases were single 19 DEL or21L858R mutation,which met the inclusion criteria for targeting sensitive genetic loci.All of them received targeted drug therapy with first/second/third-generation EGFR-TKI as first-line therapy.Patients received the third-generation EGFR-TKI osimertinib after first-line treatment with first/second-generation EGFR-TKI resistance and T790 M mutation.After being resistant to targeted drugs,patients received the treatment scheme of different PD-1 antibodies,pemetrexed and cisplatin,or that of PD-1 antibodies,pemetrexed,cisplatin and anti-angiogenesis agents in some cases.Overall,the objective response rate was 43%,the disease control rate was 67%,the progression free survival was 7.1 months,and the overall survival was 11.7 months.Subgroup analysis found the following factors have no obvious correlation with PFS(P>0.05),such as different EGFR gene mutation or PD-1 inhibitors,the model of combined therapy,with or without radiotherapy during treatment.Among them,the PFS of patients without T790 M mutation tends to be prolonged compared with those with T790 M mutation(8.7 months vs 5.1months,P=0.017).The patients were generally well tolerated,and there was no new immunotoxicity occurred.Conclusion: In the real-world,for patients with advanced NSCLC with EGFR sensitizing mutations,a combination regimen based on immune checkpoint inhibitors after targeted drugs resistance resulted in better clinical outcomes and disease control rates.The immune combination regimen was generally well tolerated with no new unknown adverse events.And no impact on clinical efficacy was observed with different EGFR gene mutation or PD-1 inhibitors,with or without radiotherapy during treatment.Patients without T790 M mutation may be an advantageous population for immune combination therapy and warrants further investigation.