Immunotherapy with chemotherapy and anti-angiogenic therapy for EGFR mutated NSCLC: challenging the dogma.

Immunotherapy with immune checkpoint inhibitors has long been associated with lack of response and efficacy in metastatic EGFR mutated non-small cell lung cancer (NSCLC). A pivotal meta-analysis demonstrated no improvement in overall survival (OS) in randomized trials comparing anti-PD -1/L1 monotherapy with docetaxel [1]. Consequently, patients harboring EGFR mutations have been excluded from most immunotherapy trials. More recently, however, there have been trials of combination chemoimmunotherapy with antiangiogenic therapy that have allowed or been conducted in patients with EGFR mutations (Table 1). The synergistic action of chemoimmunotherapy with anti-angiogenic therapy may be of particular importance, supported by a growing body of clinical and pre-clinical evidence [2]. Anti-angiogenic therapy may have immunomodulatory activity, reprogramming the tumor microenvironment (TME) from immunosuppressive to immune permissive [3].