Immunotherapy in non-small cell lung cancer harbouring driver mutations
The advent of molecular targeted therapies and the more recent introduction of immune checkpoint inhibitors (ICIs) have altered and improved the therapeutic landscape of non-small cell lung cancer (NSCLC).
ICIs confer a durable response in a subset of patients; however, their therapeutic role in oncogene-driven NSCLC remains unclear, as the vast majority of trials was conducted without patients harbouring established oncogenic mutations.
The only randomised data available on the efficacy of ICIs on oncogene addicted NSCLC come from the IMpower 150 trial and concern only EGFR mutated NSCLC patients.
At present, no biomarker is clearly predictive for response or benefit to ICIs in oncogene addicted NSCLC. These are often characterised by low tumour mutation burden (TMB) and a less inflammatory tumour microenvironment, poor in tumour-infiltrating CD8+ lymphocytes. PD-L1 can be constitutionally overexpressed without having any clinical significance.