Efficacy Analysis Of Pd-1/L1 Immune Checkpoint Inhibitors For Advanced Non-small Cell Lung Cancer After Resistance To EGFR-TKIs

BackgroundNon-small cell lung cancer(NSCLC)accounts for about 85% of all lung cancer patients,and guidelines such as NCCN recommend EGFR-driven gene testing for patients with advanced metastatic NSCLC.Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)are the first standard of care for patients with advanced NSCLC harboring EGFR-sensitive mutations.However,resistance to EGFR-TKIs is inevitable and the mechanisms of resistance vary from generation to generation,second or third generation.Follow-up therapy is currently limited for EGFR-TKIs resistant patients.Immune checkpoint inhibitors(ICIs)enable the immune system to kill tumors by enhancing their ability to recognize and kill them.Among them,programmed cell death protein 1(PD-1,PD-1)and its ligand 1(PD-1 ligand,PD-L1)inhibitors were effective and safe in selected NSCLC patients with advanced EGFR-negative mutations,but not in patients with advanced non-small cell lung cancer(NSCLC)resistant to EGFR-TKIs.Objectives1.To identify the efficacy and safety of PD-1 / L1 inhibitors in EGFR-TKIs resistant advanced NSCLC.2.Exploring factors affecting survival of EGFR-TKSI resistant patients.3.Establishment of efficacy prediction models of PD-1 / L1 inhibitors for EGFR-TKIs resistance;MethodsThis study was a single-center,retrospective analysis.One hundred and twenty-three patients with stage IV non-small cell lung cancer admitted to Shanghai Changzheng Hospital between January 2019 and January 2022 after failure of first-line EGFR-TKIs were screened by electronic medical record system.The patients were divided into ICIs combined with platinum-containing two-drug chemotherapy and anti-angiogenic drugs group(ICIs+BCP group),ICIs monotherapy group(ICIs group),and platinum-containing two-drug chemotherapy combined with anti-angiogenic drugs group(BCP group).The gender,age,smoking history,ECOG score,EGFR mutation type,PD-L1 TPS expression(TPS:percentage of PD-L1 expression on the tumor cell surface %),and the first routine blood index before second-line treatment were recorded for all enrolled patients,and CT examinations were performed every two courses to assess the effect of immunotherapy or chemotherapy on treatment.Results1.General data of all enrolled patients were counted,and a total of 123 patients diagnosed with advanced NSCLC were screened,including 64 males and 59 females.2.The differences in ORR and DCR between the ICIs+BCP group,ICIs group and BCP group were not statistically significant.median PFS(9.5 months,95% CI: 8.10-10.91 vs.4.64 months,95% CI: 3.92-5.35),OS(16.97 months,95% CI: 15.11-18.84 vs.7.9 months95% CI: 7.33-8.55),all with statistically significant differences(p<0.001).median PFS in the ICIs+BCP group compared with the BCP group(9.5 months,95% CI: 8.10-10.91 vs.6.48 months,95% CI: 5.36 to 7.60,p< 0.005),median OS(16.97 months,95% CI: 15.11-18.84 vs.11.39 months 95% CI: 9.70 to 13.08,p<0.005).3、Univariate analysis revealed that PD-L1 TPS expression,MLR,platelet count,receipt of immunotherapy,and age were significant prognostic factors affecting OS in NSCLC patients after receiving first-line EGFR-TKIs therapy resistance(p<0.05);while gender,smoking history,EGFR driver mutation type,ECOG score,neutrophil count,lymphocyte count monocyte count,NLR,and PLR were not significantly correlated with OS.4.The AUC values of the constructed Nomogram prediction model for 1-year and 2-year survival were 0.815 and 0.846.5.In the MSKCC-IMPACT cohort,a total of 332 patients with survival data and treated with ICIs were included,and OS in the ICIs combination therapy group compared with the ICIs monotherapy group(38.14 months,95% CI: 29.77-46.51 vs.24.34 months 95% CI:16.29-32.39,p=0.0416),the difference was statistically significant.Conclusions1.PD-1/L1 immune checkpoint inhibitors combined with bevacizumab in combination with platinum-containing two-drug chemotherapy are effective in patients with advanced NSCLC after resistance to EGFR-TKIs,and patient survival is better than that of conventional platinum-containing two-drug chemotherapy.2.The Nomogram prediction model can be used for survival prediction of patients with EGFR-TKIs resistance to help better individualized treatment and prognosis assessment.