Efficacy of immune checkpoint inhibitors in post-TKI NSCLC patients harboring EGFR-mutations

Abstract Objective: Immune checkpoint inhibitors (ICIs) have been validated in epidermal growth factor receptor (EGFR) wild-type advanced non-small cell lung cancer (NSCLC) patients. However, there exists no evidence regarding EGFR-mutated NSCLC patients, especially in EGFR-TKI (tyrosine kinase inhibitor) treatment failure. To address this, we collected clinical information from two cohorts and conducted a time series-based meta-analysis to determine the efficacy and safety of ICIs in patients harboring EGFR mutations.Methods: Two cohorts of 22 NSCLC patients with EGFR mutations were selected from two different hospitals. The treatment strategies and main clinical outcomes were collected and further analyzed. Meanwhile, Pubmed, Embase, and Cochrane Library were searched for relevant literature published until December 31, 2021. Endpoint outcomes included mortality and progression-free survival (PFS) at different times of follow-up. Survival rates and curve data were pooled for further analysis. To detect the data heterogeneity, subgroup analyses were conducted according to treatment strategies. Results: The two cohorts showed that the median PFS was 2.3 months (range, 1.3~6 months); and in ICI+Chemotherapy, the median PFS was 5 months (range, 0.75~9 months) (Log rank P = 0.037). Fifteen studies, including 4 trials, 10 controlled cohorts, and 1 real-world study were assessed, involving a total of ICI-treated NSCLC patients with EGFR mutation after TKI failure. The 6-month survival rate and PFS were 0.71 (95%CI: 0.62~0.78) and 0.53 (95%CI: 0.23~0.81), respectively. ICI+chemotherapy showed the best survival outcome among these groups, as demonstrated by the 12-month survival rate and PFS. Conclusions: ICI therapy may be associated with an improved prognosis of patients with EGFR mutation, especially when combined with chemotherapy. Nevertheless, current research presented a limited data size. Multicenter randomized trials are required validate ICI-based therapies for better outcome of patients harboring EGFR mutation.