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FDA Expert Panel Votes Against Keytruda Accelerated Approval for PD-L1-Positive Gastric Cancer

NEW YORK – The US Food and Drug Administration's Oncologic Drugs Advisory Committee on Thursday voted 6 to 2 against maintaining the accelerated approval for pembrolizumab (Merck's Keytruda) for patients with PD-L1-positive gastric or gastroesophageal junction cancer.

The accelerated approval, granted in 2017, made the PD-1 inhibitor available as a third-line treatment for advanced gastric and GEJ cancer patients whose tumors expressed PD-L1 with a combined positive score of at least one.

The vote to rescind the accelerated approval came this week during a multi-day meeting that was part of the FDA's effort to reevaluate multiple immunotherapy indications that were granted accelerated approval on the basis of early data. The indications evaluated failed to demonstrate benefit in later confirmatory trials.

For the gastric cancer pembrolizumab indication, the FDA had based its accelerated approval decision on a 13.3 percent observed response rate among 143 patients enrolled in a cohort within the Keynote-059 clinical trial. However, in subsequent confirmatory trials in this patient population, including Keynote-061 evaluating second-line pembrolizumab versus chemotherapy, and Keynote-062 evaluating first-line pembrolizumab versus chemotherapy, Merck's PD-1 inhibitor failed to demonstrate an overall survival benefit.

Since the 2017 approval, the FDA also highlighted, the treatment landscape for gastric cancer has changed, with other treatments, including HER2-directed therapy and additional chemotherapy regimens receiving approval. Pembrolizumab is also available to patients with gastric cancer whose tumors are microsatellite instability-high through a separate, tumor-agnostic indication.

"While we are disappointed in the outcome of the gastric cancer vote, especially given the discussion of the unmet need that remains for immunotherapy-naïve patients who have progressed to needing third-line treatment, we are committed to continuing discussions with the FDA to help ensure access to Keytruda for these patients," Roy Baynes, Merck's chief medical officer, said in a statement.