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KEYNOTE-240

Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: a randomized, double-blind, phase III trial

Phase 3N = 413NCT02702401

Population
Patients with advanced hepatocellular carcinoma previously treated with sorafenib
Design
Randomised (2:1), double-blind phase 3 trial at 119 medical centres in 27 countries; pembrolizumab plus best supportive care versus placebo plus best supportive care in patients previously treated with sorafenib. Primary end points overall survival and progression-free survival, with one-sided significance thresholds of P = 0.0174 (overall survival, final analysis) and P = 0.002 (progression-free survival, first interim analysis).
Primary endpoint
OS, PFS
Arms
  • Pembrolizumab plus best supportive care (experimental): Pembrolizumab plus best supportive care
  • Placebo plus best supportive care (control): Placebo plus best supportive care
People
Finn RS, KEYNOTE-240 investigators
OSHR 0.781 (95% CI 0.611–0.998)Δ median OS+3.3 monthsPFSHR 0.718 (95% CI 0.570–0.904)Δ median PFS+0.2 months
Show the numbers
Results reported for KEYNOTE-240
EndpointAnalysisPembrolizumab plus best supportive carePlacebo plus best supportive careEffect
OSRandomised patients as described in the abstract (analysis population not stated there)finalFinn 2020median 13.9 months (11.6–16.0)median 10.6 months (8.3–13.5)HR 0.781 (95% CI 0.611–0.998)P=0.0238One-sided P value. The prespecified one-sided significance threshold for overall survival at the final analysis was P = 0.0174, so the result did not reach it. Data cut-off 2 January 2019; median follow-up 13.8 months (pembrolizumab) and 10.6 months (placebo).
PFSRandomised patients as described in the abstract (analysis population not stated there)finalFinn 2020median 3 months (2.8–4.1)median 2.8 months (1.6–3.0)HR 0.718 (95% CI 0.570–0.904)P=0.0022Final analysis. At the first interim analysis the abstract reports median progression-free survival of 3.0 versus 2.8 months (hazard ratio 0.775, 95% CI 0.609 to 0.987; P = 0.0186) against a threshold of P = 0.002. The abstract's conclusion is that overall survival and progression-free survival did not reach statistical significance per the specified criteria.
Results reported for KEYNOTE-240
EndpointAnalysisPembrolizumab plus best supportive carePlacebo plus best supportive careEffect
OSRandomised patients as described in the abstract (analysis population not stated there)finalFinn 2020median 13.9 months (11.6–16.0)median 10.6 months (8.3–13.5)HR 0.781 (95% CI 0.611–0.998)P=0.0238One-sided P value. The prespecified one-sided significance threshold for overall survival at the final analysis was P = 0.0174, so the result did not reach it. Data cut-off 2 January 2019; median follow-up 13.8 months (pembrolizumab) and 10.6 months (placebo).
PFSRandomised patients as described in the abstract (analysis population not stated there)finalFinn 2020median 3 months (2.8–4.1)median 2.8 months (1.6–3.0)HR 0.718 (95% CI 0.570–0.904)P=0.0022Final analysis. At the first interim analysis the abstract reports median progression-free survival of 3.0 versus 2.8 months (hazard ratio 0.775, 95% CI 0.609 to 0.987; P = 0.0186) against a threshold of P = 0.002. The abstract's conclusion is that overall survival and progression-free survival did not reach statistical significance per the specified criteria.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OSPFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.7810.611–0.998
PFS0.7180.57–0.904
Illustrative — modelled from reported values, not trial data. OS, final.
0%25%50%75%100%051015202530Months (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%
963.8%55.5%
1742.8%32.9%
2627.3%18.3%
3517.5%10.1%
Illustrative — modelled from reported values, not trial data. PFS, final.
0%25%50%75%100%0246Months (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%
263.0%61.0%
439.7%37.1%
625.0%22.6%
815.7%13.8%
Primary publication: Finn RS, Ryoo BY, Merle P, Kudo M, Bouattour M, Lim HY, et al. Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial. J Clin Oncol. 2020;38(3):193-202. PubMedDOI

Appears in

Sources

  1. Finn RS, Ryoo BY, Merle P, Kudo M, Bouattour M, Lim HY, et al. Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial. J Clin Oncol. 2020;38(3):193-202.

    PubMedDOI