Oncogene-addicted non-small cell lung cancer and immunotherapy

Abstract

A majority of non-small cell lung cancer (NSCLC), especially adenocarcinomas, harbour at least one oncogenic driver mutation that can potentially be a target for therapy. The treatment of these oncogene-addicted tumors has dramatically changed the outcome of these patients, where tyrosine kinase inhibitors (TKIs) of mutated epidermal growth factor receptor (EGFR) and rearranged anaplastic lymphoma kinase (ALK) have paved the way for a new era of precision cancer medicine. Another paradigm shift in the treatment of NSCLC, as well as numerous other tumor types, has been the introduction of immunotherapy (IO) with immune checkpoint inhibitors targeting mainly programmed cell death-1 (PD-1) or its ligand PDL-L1, where studies have demonstrated an increased survival versus standard treatment with chemotherapy, both in the first- and second-line setting. However, the role of IO in oncogene-addicted NSCLC is still unclear where most clinical data come from subgroup analyses with low number of patients in larger randomized trials, and these data do not support the use of IO after TKI in this category of NSCLC patients. The purpose of this review is to summarize the existing evidence about the use of IO in oncogenicaddicted NSCLC and highlight the issues that should be addressed in the future in order to define the role of IO for these patients.