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KEYNOTE-859

Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-859/KEYNOTE-859)

Phase 3N = 1,579NCT03675737

Population
Previously untreated, histologically or cytologically confirmed locally advanced or metastatic HER2-negative gastric or gastro-oesophageal junction adenocarcinoma, ECOG performance status 0 or 1.
Design
Multicentre double-blind placebo-controlled randomised phase 3 trial at 207 centres in 33 countries. Patients were randomly assigned 1:1 to pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles, together with investigator's choice of fluorouracil plus cisplatin or capecitabine plus oxaliplatin; stratified by region, PD-L1 status and chemotherapy. Primary endpoint: overall survival in the ITT population and in the PD-L1 CPS 1 or more and CPS 10 or more populations. The abstract reports the interim analysis (median follow-up 31.0 months).
Primary endpoint
OS
Arms
  • Placebo plus chemotherapy (control, n = 789): Placebo with fluorouracil plus cisplatin or capecitabine plus oxaliplatin
  • Pembrolizumab plus chemotherapy (experimental, n = 790): Pembrolizumab 200 mg every 3 weeks with the same chemotherapy
People
Rha SY, KEYNOTE-859 investigators
OSHR 0.78 (95% CI 0.70–0.87)Δ median OS+1.4 monthsOSHR 0.74 (95% CI 0.65–0.84)Δ median OS+1.6 monthsOSHR 0.65 (95% CI 0.53–0.79)Δ median OS+3.9 months
Show the numbers
Results reported for KEYNOTE-859
EndpointAnalysisPembrolizumab plus chemotherapyPlacebo plus chemotherapyEffect
OSinterimRha 2023median 12.9 months (11.9–14.0)median 11.5 months (10.6–12.1)HR 0.78 (95% CI 0.70–0.87)P<0.0001Interim analysis; median follow-up 31.0 months (IQR 23.0-38.3).
OSPD-L1 CPS 1 or moreinterimRha 2023median 13 months (11.6–14.2)median 11.4 months (10.5–12.0)HR 0.74 (95% CI 0.65–0.84)P<0.0001
OSPD-L1 CPS 10 or moreinterimRha 2023median 15.7 months (13.8–19.3)median 11.8 months (10.3–12.7)HR 0.65 (95% CI 0.53–0.79)P<0.0001
Results reported for KEYNOTE-859
EndpointAnalysisPembrolizumab plus chemotherapyPlacebo plus chemotherapyEffect
OSinterimRha 2023median 12.9 months (11.9–14.0)median 11.5 months (10.6–12.1)HR 0.78 (95% CI 0.70–0.87)P<0.0001Interim analysis; median follow-up 31.0 months (IQR 23.0-38.3).
OSPD-L1 CPS 1 or moreinterimRha 2023median 13 months (11.6–14.2)median 11.4 months (10.5–12.0)HR 0.74 (95% CI 0.65–0.84)P<0.0001
OSPD-L1 CPS 10 or moreinterimRha 2023median 15.7 months (13.8–19.3)median 11.8 months (10.3–12.7)HR 0.65 (95% CI 0.53–0.79)P<0.0001
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OSOSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.780.7–0.87
OS0.740.65–0.84
OS0.650.53–0.79
Illustrative — modelled from reported values, not trial data. OS, interim.
0%25%50%75%100%051015202530Months (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%
865.1%61.7%
1642.3%38.1%
2427.5%23.5%
3217.9%14.5%
Illustrative — modelled from reported values, not trial data. OS, interim.
0%25%50%75%100%051015202530Months (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%
865.3%61.5%
1642.6%37.8%
2427.8%23.2%
3317.2%13.4%
Primary publication: Rha SY, Oh DY, Yañez P, Bai Y, Ryu MH, Lee J, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2023;24(11):1181-1195. PubMedDOI

Appears in

Sources

  1. Rha SY, Oh DY, Yañez P, Bai Y, Ryu MH, Lee J, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2023;24(11):1181-1195.

    PubMedDOI