Oncologists and multidisciplinary teams treating adults with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma whose tumors express PD-L1 (CPS ≥1) should note pembrolizumab is now FDA-approved in combination with trastuzumab and fluoropyrimidine- and platinum-containing chemotherapy as a first-line option ^[4][7]. The approval is supported by KEYNOTE-811 data showing improved PFS and OS in the PD-L1 CPS ≥1 subgroup, and selection requires an FDA-authorized PD-L1 test such as the Agilent PD-L1 IHC 22C3 pharmDx ^[4][5]. Which patient subgroups defined by levels of PD-L1 expression or comorbidities derive the largest absolute benefit from adding pembrolizumab remains a practical question for routine care?

Q1 What is pembrolizumab (Keytruda) approved for in gastric/GEJ cancer?

Pembrolizumab is approved in combination 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 PD-L1 (CPS ≥1) as determined by an FDA-authorized test. This approval was granted by the FDA on March 19, 2025 based on KEYNOTE-811 results.

Q2 How does pembrolizumab work?

Pembrolizumab is a programmed death receptor-1 (PD-1) blocking monoclonal antibody that binds PD-1 and blocks its interaction with PD-L1 and PD-L2, thereby releasing PD-1 pathway–mediated inhibition of the immune response and facilitating anti-tumor immune activity. The mechanism and class are described in KEYTRUDA prescribing information.

Q3 What is the recommended dose of pembrolizumab for this indication?

The recommended pembrolizumab dose in combination with trastuzumab and chemotherapy is 200 mg every 3 weeks or 400 mg every 6 weeks administered intravenously until disease progression, unacceptable toxicity, or up to 24 months, consistent with the prescribing information. Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the common side effects observed with pembrolizumab in combination with trastuzumab and chemotherapy?

The adverse reaction profile reported with pembrolizumab plus trastuzumab and chemotherapy in KEYNOTE-811 was consistent with known pembrolizumab safety data and included events such as fatigue, musculoskeletal pain, nausea, rash, diarrhea, pyrexia, cough, decreased appetite, pruritus, dyspnea, constipation, generalized pain, abdominal pain, and hypothyroidism. Immune-mediated adverse reactions and other warnings described in the prescribing information should be reviewed prior to treatment initiation.

Clinicians should consult current prescribing information for complete dosing guidance.