Pembrolizumab monotherapy for PD-L1 ≥50% non-small cell lung cancer, undisputed first choice?
The recent introduction of immunotherapy has drastically changed the treatment landscape of patients with advanced non-small cell lung cancer (NSCLC). Approval by the US Food and Drug Administration and the European Medicines Agency of immune checkpoint inhibitors (ICIs) soon followed after several phase III trials showed superior overall survival (OS) of the monoclonal antibody therapy directed against the PD-1 receptor (nivolumab and pembrolizumab) and its ligand PD-L1 (atezolizumab) over previously standard of care (SoC) docetaxel (1-5). In first-line setting, the randomized phase III KEYNOTE-024 trial was the first study to show an OS benefit of pembrolizumab over platinum-doublet chemotherapy in treatment-naïve patients with metastatic NSCLC harbouring a PD-L1 tumor proportion score (TPS) of ≥50% (HR 0.60; 95% CI, 0.41–0.89; P=0.005) (6). At the second interim analysis the primary endpoint—progression free survival (PFS)—was reached and the trial was prematurely stopped. This resulted in approval for first-line treatment with pembrolizumab for advanced NSCLC with a TPS of ≥50%.