# KEYNOTE-859: pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer

Source: https://onco.cc/key-papers/paper-keynote-859-lancet-oncol-2023/  
OnCo record `paper-keynote-859-lancet-oncol-2023` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Adding pembrolizumab to platinum-fluoropyrimidine chemotherapy lengthened survival in HER2-negative advanced gastric cancer, with the largest gain in tumours with a PD-L1 combined positive score of 10 or more, confirming chemo-immunotherapy as first-line standard.

## Summary

Phase 3 placebo-controlled trial of 1,579 patients with untreated HER2-negative locally advanced or metastatic gastric or junctional adenocarcinoma randomised to pembrolizumab or placebo with fluoropyrimidine-platinum chemotherapy.

Median overall survival was 12.9 versus 11.5 months overall (hazard ratio 0.78), 13.0 versus 11.4 months in combined positive score 1 or more (hazard ratio 0.74) and 15.7 versus 11.8 months in score 10 or more (hazard ratio 0.65).

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: The Lancet Oncology
- Year: 2023
- DOI: 10.1016/S1470-2045(23)00515-6
- Authors: Rha SY, Oh DY, Yañez P, et al.
- Findings: Median overall survival 12.9 vs 11.5 months overall; hazard ratio 0.78.; Combined positive score 10 or more: 15.7 vs 11.8 months; hazard ratio 0.65.
- What it means: Pembrolizumab plus chemotherapy is approved for HER2-negative advanced gastric cancer, alongside nivolumab plus chemotherapy from CheckMate 649, with strongest evidence at higher PD-L1 scores.
- Caveats: Benefit in PD-L1-low tumours is small, and European approval is restricted to combined positive score 1 or more.

## Sources

- Lancet Oncol 2023: https://doi.org/10.1016/S1470-2045(23)00515-6
- PubMed: https://pubmed.ncbi.nlm.nih.gov/37875143/

## Connected records

- cancers: [PD-L1-high gastric cancer](https://onco.cc/cancers/gastric-pdl1-high/)
- drugs: [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- trials: [KEYNOTE-859](https://onco.cc/trials/keynote-859/)
- journals: [The Lancet Oncology](https://onco.cc/journals/lancet-oncology/)

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