KEYNOTE-042 rolls back programmed cell death ligand 1 threshold for non-small cell lung cancer pembrolizumab monotherapy without new insight into those deriving benefit

The past two years have been exceptional for pembrolizumab in advanced non-small cell lung cancer (NSCLC). The publication of KEYNOTE-189 redefined first-line treatment with combination chemotherapy and pembrolizumab as a new standard-of-care in an unselected population, KEYNOTE-042 expanded the United States Food & Drug Administration (FDA)’s approval for first-line pembrolizumab monotherapy, and KEYNOTE-001 showed the most robust five-year overall survival (OS) results ever seen in advanced NSCLC, specifically among patients with high programmed cell death ligand 1 (PD-L1) expression ( Table 1 ) (1-4).