Keytruda Receives Traditional Approval for Some Patients With HER2-Positive Gastric or GEJ Adenocarcinoma

Originally published by our sister publication Clinical Oncology News

By Clinical Oncology News Staff

The FDA has granted traditional approval to pembrolizumab (Keytruda, Merck) with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express programmed death ligand-1 (PD-L1) (combined positive score [CPS] ≥1).

Pembrolizumab previously received accelerated approval for this indication on May 5, 2021, based on interim analysis of the trial described below.

Efficacy was evaluated in KEYNOTE-811 (ClinicalTrials.gov. Identifier: NCT03615326), a multicenter, randomized, double-blind, placebo-controlled trial enrolling 698 patients with HER2-positive advanced gastric or GEJ adenocarcinoma not previously treated with systemic therapy for metastatic disease. Among the 698 patients, 594 (85%) had tumors expressing PD-L1 with a CPS of at least 1 using the PD-L1 IHC 22C3 pharmDx kit (Agilent). Patients were randomized (1:1) to pembrolizumab 200 mg or placebo, in combination with trastuzumab and either 5-fluorouracil plus cisplatin or capecitabine plus oxaliplatin.

The major efficacy outcome measures assessed were progression-free survival (PFS) by blinded independent central review and overall survival (OS). Additional outcome measures included overall response rate (ORR) and duration of response (DOR). A statistically significant improvement in OS and PFS was demonstrated in patients randomized to pembrolizumab in combination with trastuzumab and chemotherapy compared with placebo in combination with trastuzumab and chemotherapy. In patients with tumors expressing PD-L1 with a CPS of at least 1, median PFS was 10.9 months (95% CI, 8.5-12.5 months) in the pembrolizumab arm and 7.3 months (95% CI, 6.8- 8.4 months) in the placebo arm (hazard ratio [HR], 0.72; 95% CI, 0.60-0.87). Median OS was 20.1 months (95% CI, 17.9-22.9 months) and 15.7 months (95% CI, 13.5-18.5 months) in the respective arms (HR, 0.79; 95% CI, 0.66-0.95]. ORR was 73% (95% CI, 68%-78%) and 58% (95% CI, 53%-64%), and median DOR was 11.3 months (95% CI, 9.9-13.7 months) and 9.6 months (95% CI, 7.1-11.2 months).

The adverse reaction profile observed in patients receiving pembrolizumab was consistent with its known safety profile.

The full prescribing information for pembrolizumab will be posted on Drugs@FDA.

Based on a press release from the FDA.