NEW YORK – Merck said on Friday that it will voluntarily withdraw its accelerated approval indication for pembrolizumab (Keytruda) as a third-line treatment for patients with advanced, PD-L1-expressing gastric or gastroesophageal junction (GEJ) cancer.
The accelerated approval, which the US Food and Drug Administration granted in 2017, made the checkpoint inhibitor available to patients whose tumors expressed PD-L1 with a combined positive score of at least one. The agency expedited approval of the drug based on its ability to shrink tumors in the 143-patient Keynote-059 trial. In that study, the objective response rate was 13.3 percent in pembrolizumab-treated patients.
At the time, the FDA stipulated that Merck would need to conduct confirmatory trials demonstrating the agent's overall survival benefit in this patient population if it wanted to convert the accelerated approval to a full approval. Now, evidence from those confirmatory trials — including Keynote-061 evaluating second-line pembrolizumab versus chemotherapy, as well as Keynote-062 evaluating first-line pembrolizumab versus chemotherapy — have shown that Merck's checkpoint inhibitor does not confer an overall survival benefit for these patients.
In light of these findings, the FDA's Oncologic Drug Advisory Committee convened in late April to vote on whether to keep the drug on the market for this indication. The panel voted 6 to 2 to rescind the accelerated approval due to the lack of overall survival benefit seen in subsequent trials and the availability of newer gastric cancer treatment options since 2017.
Patients now have access to HER2-directed therapy and to pembrolizumab for refractory tumors with high microsatellite instability. Less than a week after the advisory committee's vote, the agency also approved pembrolizumab plus trastuzumab (Genentech's Herceptin) and chemotherapy as a first-line treatment for patients with advanced, HER2-positive gastric or GEJ cancer.
Merck will officially withdraw the accelerated approval six months from now and said in a statement that patients receiving pembrolizumab in this setting should discuss their treatment options with their oncologists.