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
Year: 2019
Type: article
Abstract: 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).As we have suggested previously, KEYNOTE trials have benefited from being carefully tailored with preplanned analyses with PD-L1 immunohistochemistry (IHC) tumor proportion score (TPS) cutoffs using the 22C3 pharmDx assay (Agilent Technologies, Carpinteria, CA, USA) (5,6).Yet while these trials suggest that PD-L1 TPS ≥50% remains the most reliable biomarker for durable response with pembrolizumab, what to do with PD-L1 TPS scores less than 50% continues to be challenging.Does a 1% difference really change clinical outcome?KEYNOTE-042 attempted to answer this question in the case of pembrolizumab monotherapy compared to standard chemotherapy (2).Randomizing over 1,200 patients with PD-L1 TPS ≥1% in 213 medical centers in 32 countries around the world, it is one of the largest studies
Authors: Amy Lauren Cummings, Edward B. Garon
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W2964633153