On March 1, Merck announced the company is voluntarily withdrawing the U.S. indication for pembrolizumab (Keytruda) for the treatment of patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy. The withdrawal of this indication was done in consultation with the U.S. Food and Drug Administration (FDA), and Merck is working to complete this process over the coming weeks. This decision does not affect other indications for pembrolizumab.
Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes, which may affect both tumor cells and healthy cells.
The accelerated approval for pembrolizumab was granted in June 2019 based on tumor response rate and durability of response data from KEYNOTE-158 (cohort G) and KEYNOTE-028 (cohort C1). Continued approval for this indication was contingent upon completion of the postmarketing requirement establishing superiority of pembrolizumab as determined by overall survival. The confirmatory phase III trial for this indication, KEYNOTE-604, met one of its dual primary endpoints of progression-free survival but did not reach statistical significance for the other primary endpoint of overall survival.
Merck's consultation with the FDA on this withdrawal is part of an industry-wide evaluation of indications based on accelerated approvals that have not yet met their postmarketing requirements. Merck is notifying health-care professionals about this withdrawal. Patients being treated with pembrolizumab for their metastatic small cell lung cancer should discuss their care with their health-care provider.
