FDA amends pembrolizumab’s gastric cancer indication
Regulatory approval news: On Nov 7, 2023, the FDA revised the accelerated approval indication for pembrolizumab (Keytruda) given with trastuzumab plus fluoropyrimidine- and platinum-containing chemotherapy as first-line treatment for locally advanced unresectable or metastatic HER2-positive gastric/GEJ adenocarcinoma. Use is now restricted to tumors with PD-L1 expression (CPS ≥1) determined by an FDA-approved test. FDA also approved Agilent PD-L1 IHC 22C3 pharmDx as a companion diagnostic.
FDA amends pembrolizumab gastric/GEJ adenocarcinoma indication (accelerated approval)
On Nov 7, 2023, the FDA revised the existing accelerated approval indication for pembrolizumab (Keytruda) in combination with trastuzumab, fluoropyrimidine, and platinum-containing chemotherapy for first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. The updated indication restricts use to patients whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
The FDA also approved Agilent PD-L1 IHC 22C3 pharmDx as a companion diagnostic to select patients with gastric/GEJ adenocarcinoma whose tumors have PD-L1 CPS ≥1.
Efficacy was evaluated in KEYNOTE-811 (NCT03615326), a multicenter, randomized, double-blind, placebo-controlled trial in previously untreated metastatic HER2-positive gastric/GEJ adenocarcinoma. In the May 5, 2021 interim analysis (first 264 randomized), ORR was 74% (95% CI 66–82) with pembrolizumab-containing therapy vs 52% (95% CI 43–61) with placebo-containing therapy (p<0.0001); median DOR was 10.6 vs 9.5 months, respectively.
In a prespecified interim analysis of the fully enrolled trial (N=698), subgroup results for PD-L1 CPS <1 (N=104) showed OS HR 1.41 (95% CI 0.90–2.20) and PFS HR 1.03 (95% CI 0.65–1.64).
Safety was generally consistent with known profiles of pembrolizumab and trastuzumab + chemotherapy.