Immunotherapy-based therapy as a promising treatment for EGFR-mutant advanced non-small cell lung cancer patients after EGFR-TKI resistance

Traditionally, epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) has been regarded as a cold tumor based on the immunosuppressive tumor immune microenvironment (TIME). However, recent studies have found that EGFR-tyrosine kinase inhibitor (EGFR-TKI) treatment could shift host immunity from immunosuppressive to immunosupportive TIME, which has renewed hopes of immunotherapy.In this review, we highlight five main immunotherapy-based therapies for patients after EGFR-TKI failure, including safety and efficacy data from prospective and retrospective clinical studies.The efficacy of immunotherapy alone is extremely limited. Immunotherapy plus chemotherapy show an ORR of 29.5%-59.3% and an mPFS of about 7 months. There is still scarce evidence for immunotherapy plus antiangiogenesis therapy. A combination of immunotherapy with EGFR-TKIs exhibits higher treatment-related adverse events and lower clinical outcomes compared to EGFR-TKI alone. Importantly, immunotherapy plus antiangiogenesis and chemotherapy achieves an mPFS of 6.9-10.2 months. In general, the strategy of combining immunotherapy with chemotherapy and/or an antiangiogenic drug is a novel and promising method for treating advanced NSCLC after EGFR-TKI failure. Therefore, the dominant population of EGFR-TKI resistant patients were characterized by EGFR uncommon mutation, EGFR L858R mutation, PD-L1 ≥ 50%, prior antiangiogenic drugs, and negative T790 M mutation for immunotherapy-based therapy.