KEYNOTE-811

In first-line HER2-positive advanced gastric/GEJ adenocarcinoma with PD-L1 CPS ≥1, does pembrolizumab added to trastuzumab and chemotherapy improve outcomes?

Evidence snapshot updated 23 October 2026. Source links are provided below; this is an evidence summary, not a substitute for current local guidelines or individual clinical judgement.

Population and treatment

698 patients with previously untreated HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma; current US traditional approval applies to PD-L1 CPS ≥1.

Intervention and comparator: Pembrolizumab 200 mg IV every 3 weeks (or approved equivalent schedule) plus trastuzumab and fluoropyrimidine/platinum chemotherapy versus placebo plus trastuzumab and the same chemotherapy.

ClinicalTrials.gov: NCT03615326 ↗

Key results

In the PD-L1 CPS ≥1 population, median OS was 20.1 vs 15.7 months (HR 0.79, 95% CI 0.66–0.95). Median PFS was 10.9 vs 7.3 months (HR 0.72, 95% CI 0.60–0.87); ORR 73.2% vs 58.4%.

Overall survival · Median OS; final analysis

Absolute-effect interpretation: Median OS difference 4.4 months is not an NNT. Use the CPS ≥1 population for the current US indication; do not substitute overall-population values for biomarker-defined estimates.

Toxicity and treatment burden

Immune-mediated toxicities are added to chemotherapy/trastuzumab burdens; monitor cardiac function, diarrhoea, rash, thyroid function, hepatitis and pneumonitis. Review the full label for rare fatal immune-mediated events.

Interpretation and limitations

The treatment question is biomarker- and HER2-specific. KEYNOTE-811 is not evidence for adding pembrolizumab to HER2-negative gastric cancer or for all PD-L1-negative HER2-positive patients. Regulatory indications can differ by jurisdiction.

Use endpoint definitions, follow-up, analysis population and comparator exactly as reported. Do not infer NNT from a hazard ratio or median survival. Subgroup findings should not be treated as predictive unless the trial design and interaction testing support that interpretation.

Primary source and further reading

Primary publication / authoritative source ↗

Trial registry (NCT03615326) ↗

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