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KEYNOTE-394

Pembrolizumab versus placebo as second-line therapy in patients from Asia with advanced hepatocellular carcinoma: a randomized, double-blind, phase III trial

Phase 3N = 453NCT03062358

Population
Patients from Asia with advanced hepatocellular carcinoma and progression during or after, or intolerance of, sorafenib or oxaliplatin-based chemotherapy
Design
Double-blind phase 3 trial; patients from Asia randomly assigned 2:1 to pembrolizumab 200 mg or placebo once every 3 weeks for up to 35 cycles plus best supportive care. Primary end point overall survival (one-sided significance threshold P = 0.0193, final analysis); secondary end points included progression-free survival and objective response rate (RECIST 1.1, blinded independent central review).
Primary endpoint
OS
Arms
  • Pembrolizumab plus best supportive care (experimental, n = 300): Pembrolizumab 200 mg once every 3 weeks for up to 35 cycles
  • Placebo plus best supportive care (control, n = 153): Placebo once every 3 weeks for up to 35 cycles
People
Qin S
OSHR 0.79 (95% CI 0.63–0.99)Δ median OS+1.6 monthsPFSHR 0.74 (95% CI 0.60–0.92)Δ median PFS+0.3 monthsΔ ORR+11.4 points
Show the numbers
Results reported for KEYNOTE-394
EndpointAnalysisPembrolizumab plus best supportive carePlacebo plus best supportive careEffect
OSfinalQin 2023median 14.6 monthsmedian 13 monthsHR 0.79 (95% CI 0.63–0.99)P=0.0180One-sided P value; below the prespecified final-analysis threshold of P = 0.0193. Final analysis data cut-off 30 June 2021; median follow-up 33.8 months.
PFSinterimQin 2023median 2.6 monthsmedian 2.3 monthsHR 0.74 (95% CI 0.60–0.92)P=0.0032Secondary end point; second interim analysis (data cut-off 30 June 2020); one-sided P value below the prespecified boundary of P = 0.0134.
ORRinterimQin 202312.7% (9.1–17.0%)1.3% (0.2–4.6%)P<0.0001Secondary end point; blinded independent central review, RECIST 1.1.
Results reported for KEYNOTE-394
EndpointAnalysisPembrolizumab plus best supportive carePlacebo plus best supportive careEffect
OSfinalQin 2023median 14.6 monthsmedian 13 monthsHR 0.79 (95% CI 0.63–0.99)P=0.0180One-sided P value; below the prespecified final-analysis threshold of P = 0.0193. Final analysis data cut-off 30 June 2021; median follow-up 33.8 months.
PFSinterimQin 2023median 2.6 monthsmedian 2.3 monthsHR 0.74 (95% CI 0.60–0.92)P=0.0032Secondary end point; second interim analysis (data cut-off 30 June 2020); one-sided P value below the prespecified boundary of P = 0.0134.
ORRinterimQin 202312.7% (9.1–17.0%)1.3% (0.2–4.6%)P<0.0001Secondary end point; blinded independent central review, RECIST 1.1.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OSPFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.790.63–0.99
PFS0.740.6–0.92
Illustrative — modelled from reported values, not trial data. OS, final.
0%25%50%75%100%0102030Months (modelled)
  • Pembrolizumab plus best supportive care (experimental)
  • Placebo plus best supportive care (control)

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

Data table (modelled values)
MonthsPembrolizumab plus best supportive carePlacebo plus best supportive care
0100.0%100.0%
965.2%61.9%
1842.5%38.3%
2727.8%23.7%
3717.3%13.9%
Illustrative — modelled from reported values, not trial data. PFS, interim.
0%25%50%75%100%0123456Months (modelled)
  • Pembrolizumab plus best supportive care (experimental)
  • Placebo plus best supportive care (control)

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

Data table (modelled values)
MonthsPembrolizumab plus best supportive carePlacebo plus best supportive care
0100.0%100.0%
258.7%54.7%
344.9%40.5%
526.4%22.2%
715.5%12.1%
Primary publication: Qin S, Chen Z, Fang W, Ren Z, Xu R, Ryoo BY, et al. Pembrolizumab Versus Placebo as Second-Line Therapy in Patients From Asia With Advanced Hepatocellular Carcinoma: A Randomized, Double-Blind, Phase III Trial. J Clin Oncol. 2023;41(7):1434-1443. PubMedDOI

Appears in

Sources

  1. Qin S, Chen Z, Fang W, Ren Z, Xu R, Ryoo BY, et al. Pembrolizumab Versus Placebo as Second-Line Therapy in Patients From Asia With Advanced Hepatocellular Carcinoma: A Randomized, Double-Blind, Phase III Trial. J Clin Oncol. 2023;41(7):1434-1443.

    PubMedDOI