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KEYNOTE-585

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Pembrolizumab Plus Chemotherapy Versus Chemotherapy as Perioperative Therapy in Locally Advanced Gastric and Gastroesophageal Junction Cancer: Final Analysis of the Randomized, Phase III KEYNOTE-585 Study

Phase 3N = 1,007NCT03221426

Population
Participants with previously untreated, locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma: main cohort (n = 804) and FLOT cohort (n = 203).
Design
Randomised phase 3 trial of neoadjuvant and adjuvant pembrolizumab plus chemotherapy versus placebo plus chemotherapy (1:1) in previously untreated, locally advanced, resectable gastric or GEJ cancer. A main cohort (n = 804) and a separate FLOT cohort (n = 203) were enrolled; ClinicalTrials.gov enrolment 1007 equals 804 plus 203. Primary endpoints per the abstract: pathologic complete response (central review), event-free survival (investigator), overall survival and safety. The data here are from the final analysis report; the earlier interim report is not summarised.
Primary endpoint
pCR, EFS, OS
Arms
  • Placebo plus chemotherapy (control): Placebo with perioperative chemotherapy
  • Pembrolizumab plus chemotherapy (experimental): Pembrolizumab with perioperative chemotherapy, then adjuvant pembrolizumab
People
Shitara K, senior author KEYNOTE-585 Investigators
OSHR 0.86 (95% CI 0.71–1.06)Δ median OS+16.1 monthsEFSHR 0.81 (95% CI 0.67–0.98)
Show the numbers
Results reported for KEYNOTE-585
EndpointAnalysisPembrolizumab plus chemotherapyPlacebo plus chemotherapyEffect
OSMain cohort (n = 804)finalmedian follow-up 59.9 monthsShitara 2025median 71.8 monthsmedian 55.7 monthsHR 0.86 (95% CI 0.71–1.06)The 95% confidence interval of the hazard ratio includes 1. Median follow-up range 39 to 76 months.
EFSNot stated in the abstract (reported after the main-cohort OS result)finalShitara 2025——HR 0.81 (95% CI 0.67–0.98)The abstract describes the event-free survival result as a trend toward longer EFS.
Results reported for KEYNOTE-585
EndpointAnalysisPembrolizumab plus chemotherapyPlacebo plus chemotherapyEffect
OSMain cohort (n = 804)finalmedian follow-up 59.9 monthsShitara 2025median 71.8 monthsmedian 55.7 monthsHR 0.86 (95% CI 0.71–1.06)The 95% confidence interval of the hazard ratio includes 1. Median follow-up range 39 to 76 months.
EFSNot stated in the abstract (reported after the main-cohort OS result)finalShitara 2025——HR 0.81 (95% CI 0.67–0.98)The abstract describes the event-free survival result as a trend toward longer EFS.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OSEFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.860.71–1.06
EFS0.810.67–0.98
Illustrative — modelled from reported values, not trial data. OS, final.
0%25%50%75%100%050100150Months (modelled)
  • Pembrolizumab plus chemotherapy (experimental)
  • Placebo plus chemotherapy (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsPembrolizumab plus chemotherapyPlacebo plus chemotherapy
0100.0%100.0%
4564.8%57.1%
9041.9%32.6%
13527.2%18.6%
18017.6%10.6%
Primary publication: Shitara K, Rha SY, Wyrwicz L, Oshima T, Karaseva N, Osipov M, et al. Pembrolizumab Plus Chemotherapy Versus Chemotherapy as Perioperative Therapy in Locally Advanced Gastric and Gastroesophageal Junction Cancer: Final Analysis of the Randomized, Phase III KEYNOTE-585 Study. J Clin Oncol. 2025;43(29):3152-3159. PubMedDOI

Appears in

Sources

  1. Shitara K, Rha SY, Wyrwicz L, Oshima T, Karaseva N, Osipov M, et al. Pembrolizumab Plus Chemotherapy Versus Chemotherapy as Perioperative Therapy in Locally Advanced Gastric and Gastroesophageal Junction Cancer: Final Analysis of the Randomized, Phase III KEYNOTE-585 Study. J Clin Oncol. 2025;43(29):3152-3159.

    PubMedDOI