FDA amends gastric cancer indication for Keytruda
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The FDA revised an existing indication of pembrolizumab for the first-line treatment of certain patients with gastric or gastroesophageal junction adenocarcinoma.
The prior approved indication included the use of pembrolizumab (Keytruda, Merck) in combination with trastuzumab (Herceptin, Genentech) and fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma.
However, the updated indication under accelerated approval regulations restricts its use to patients whose tumors express PD-L1 (combined positive score 1 or higher) as shown by an FDA-approved test.
The agency based the revised indication on results from the randomized, double-blind KEYNOTE-811 study, which assessed efficacy among patients with HER2-positive locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma who had not received prior systemic therapy for metastatic disease.
Researchers randomly assigned patients in a 1:1 ratio to receive trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin, with 200 mg pembrolizumab delivered intravenously or placebo every 2 weeks.
FDA based the original approval on interim analysis of objective response rate and duration of response (DOR), which researchers assessed on data from the first 264 patients; results showed ORR to be 74% (95% CI, 66-82) in the pembrolizumab plus chemotherapy arm and 52% (95% CI, 43-61) in the placebo plus chemotherapy arm, with a median DOR of 10.6 months (95% CI, 1.1–16.5) in the investigative arm and 9.5 months (95% CI, 1.4–15.4) in the placebo arm.
However, a recent prespecified analysis of the fully enrolled trial (n = 698) revealed a hazard ratio of 1.41 (95% CI, 0.9–2.2) for OS and 1.03 (95% CI, 0.65–1.64) for PFS among patients with a PD-L1 combined positive score of less than1.
Researchers noted that the safety profile among patients treated with the investigative arm appeared “generally consistent” with each agent’s known safety profiles.
The FDA also approved Agilent PD-L1 IHC 22C3 pharmDx as a companion diagnostic assay to determine individuals who are eligible for treatment with pembrolizumab for gastric cancer based on PD-L1 tumor expression.
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