Pembrolizumab immunotherapy received FDA approval for HER2-positive gastric cancer treatment

Of gastric and gastroesophageal junction cancers, 15% to 20 overexpress human epidermal growth factor receptor 2 (HER2) on the cancer cell surface; these are called HER2-positive gastric cancer. For patients with advanced HER2-positive gastric cancer, the standard treatment until this approval was treatment line 1. This was chemotherapy plus the long-used anti-HER2 trastuzumab antibody.

Important update dated 19 March 2025

On 19 March 2025, the FDA (US Food and Drug Administration) granted, for first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma, pembrolizumab (Keytruda) combined with trastuzumab, a fluoropyrimidine and platinum-containing chemotherapy full approval. This approval applies to patients whose tumors express PD-L1 (CPS ≥1) at the indicated expression level.

The FDA had previously approved pembrolizumab on 5 May 2021 under accelerated approval based on overall response rate results. The traditional approval dated 19 March 2025 is based on final data (overall survival) from the KEYNOTE-811 study, providing stronger evidence of pembrolizumab’s efficacy and safety.

Previous update dated 07.11.2023

On 7 November 2023, the FDA had revised the existing indication for pembrolizumab as first-line treatment for patients with the same condition. The previous updated indication, which remained approved under accelerated approval regulations, restricted its use to patients whose tumors expressed PD-L1 (CPS ≥ 1), as determined by an FDA-approved test. Previously, PD-L1 positivity had not been required.

FDA approval based on the KEYNOTE-811 study

The approval is based on the multicenter, randomized, double-blind, placebo-controlled KEYNOTE-811 study in patients with HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma. The study included 698 patients who had not received systemic treatment. Of these patients, 594 (85%) had tumors with PD-L1 CPS ≥1.

Patients were randomly assigned 1:1 to two groups receiving:

• Pembrolizumab (200 mg) or placebo + trastuzumab and a fluoropyrimidine with platinum-based chemotherapy as a combination.

The study’s main results:

• Median progression-free survival (PFS):

  • In the pembrolizumab arm 10.9 months (95% CI: 8.5, 12.5)

  • In the placebo arm 7.3 months (95% CI: 6.8, 8.4)

  • Hazard ratio (HR): 0.72 (95% CI: 0.60, 0.87)

• Median overall survival:

  • In the pembrolizumab arm 20.1 months (95% CI: 17.9, 22.9)

  • In the placebo arm 15.7 months (95% CI: 13.5, 18.5)

  • HR: 0.79 (95% CI: 0.66, 0.95)

• Overall response rate:

  • In the pembrolizumab arm 73% (95% CI: 68, 78)

  • In the placebo arm 58% (95% CI: 53, 64)

• Median duration of response:

  • In the pembrolizumab arm 11.3 months (95% CI: 9.9, 13.7)

  • In the placebo arm 9.6 months (95% CI: 7.1, 11.2)

These data show that pembrolizumab, when used in combination with trastuzumab and chemotherapy, significantly improves overall survival and progression-free survival.

Adverse effects and safety

The adverse reaction profile observed in patients receiving pembrolizumab in the study is consistent with the previously known safety profile of pembrolizumab.

Dose

For adult patients with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma, the recommended pembrolizumab dose in combination with trastuzumab and chemotherapy is:

• 200 mg every 3 weeks or

• 400 mg every 6 weeks.

This traditional approval further strengthens pembrolizumab’s place in HER2-positive gastric cancer treatment. Clinical data demonstrate that this combination treatment extends survival and provides an important benefit for patients.