Overview of Systematic Reviews of Immune Checkpoint Inhibitors in Non–Small-Cell Lung Cancer with EGFR, ALK, ROS1, and RET Actionable Driver Mutations

This review evaluated the efficacy and safety of immune checkpoint inhibitors as monotherapy in patients with previously treated advanced or metastatic non–small-cell lung cancer (NSCLC) harbouring EGFR, ALK, ROS1, or RET mutations. Thirteen systematic reviews of randomized controlled trials were assessed, revealing critical methodological flaws. All reviews focused on survival outcomes for patients with NSCLC  with EGFR mutations, relying on the same set of 4 clinical trials, and largely overlooked other outcomes or patient groups. Importantly, no evidence was found regarding the efficacy and safety of immune checkpoint inhibitors in patients with ALK, ROS1, or RET mutations. The reviews generally concluded that immune checkpoint inhibitors do not significantly improve overall survival or progression-free survival compared to chemotherapy in patients with EGFR mutations. Additionally, no conclusions could be drawn about benefits based on histology or anti–programmed cell death 1 ligand 1 (PD-L1) expression levels, and safety assessments were inadequate due to a lack of evidence.