Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Clinical Oncology Année : 2020

Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial

Richard Finn
  • Fonction : Auteur
Baek-Yeol Ryoo
  • Fonction : Auteur
Masatoshi Kudo
  • Fonction : Auteur
Mohamed Bouattour
  • Fonction : Auteur
Ho Yeong Lim
  • Fonction : Auteur
Valeriy Breder
  • Fonction : Auteur
Julien Edeline
  • Fonction : Auteur
Yee Chao
  • Fonction : Auteur
Sadahisa Ogasawara
  • Fonction : Auteur
Thomas Yau
  • Fonction : Auteur
Marcelo Garrido
  • Fonction : Auteur
Stephen Chan
  • Fonction : Auteur
Jennifer Knox
  • Fonction : Auteur
Bruno Daniele
  • Fonction : Auteur
Scot Ebbinghaus
  • Fonction : Auteur
Erluo Chen
  • Fonction : Auteur
Abby Siegel
  • Fonction : Auteur
Andrew Zhu
  • Fonction : Auteur
Ann-Lii Cheng
  • Fonction : Auteur

Résumé

PURPOSE Pembrolizumab demonstrated antitumor activity and safety in the phase II KEYNOTE-224 trial in previously treated patients with advanced hepatocellular carcinoma (HCC). KEYNOTE-240 evaluated the efficacy and safety of pembrolizumab in this population. PATIENTS AND METHODS This randomized, double-blind, phase III study was conducted at 119 medical centers in 27 countries. Eligible patients with advanced HCC, previously treated with sorafenib, were randomly assigned at a two-to-one ratio to receive pembrolizumab plus best supportive care (BSC) or placebo plus BSC. Primary end points were overall survival (OS) and progression-free survival (PFS; one-sided significance thresholds, P = .0174 [final analysis] and P = .002 [first interim analysis], respectively). Safety was assessed in all patients who received ≥ 1 dose of study drug. RESULTS Between May 31, 2016, and November 23, 2017, 413 patients were randomly assigned. As of January 2, 2019, median follow-up was 13.8 months for pembrolizumab and 10.6 months for placebo. Median OS was 13.9 months (95% CI, 11.6 to 16.0 months) for pembrolizumab versus 10.6 months (95% CI, 8.3 to 13.5 months) for placebo (hazard ratio [HR], 0.781; 95% CI, 0.611 to 0.998; P = .0238). Median PFS for pembrolizumab was 3.0 months (95% CI, 2.8 to 4.1 months) versus 2.8 months (95% CI, 2.5 to 4.1 months) for placebo at the first interim analysis (HR, 0.775; 95% CI, 0.609 to 0.987; P = .0186) and 3.0 months (95% CI, 2.8 to 4.1 months) versus 2.8 months (95% CI, 1.6 to 3.0 months) at final analysis (HR, 0.718; 95% CI, 0.570 to 0.904; P = .0022). Grade 3 or higher adverse events occurred in 147 (52.7%) and 62 patients (46.3%) for pembrolizumab versus placebo; those that were treatment related occurred in 52 (18.6%) and 10 patients (7.5%), respectively. No hepatitis C or B flares were identified. CONCLUSION In this study, OS and PFS did not reach statistical significance per specified criteria. The results are consistent with those of KEYNOTE-224, supporting a favorable risk-to-benefit ratio for pembrolizumab in this population.

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Cancer
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Dates et versions

hal-04160412 , version 1 (12-07-2023)

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Richard Finn, Baek-Yeol Ryoo, Philippe Merle, Masatoshi Kudo, Mohamed Bouattour, et al.. Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial. Journal of Clinical Oncology, 2020, 38 (3), pp.193-202. ⟨10.1200/JCO.19.01307⟩. ⟨hal-04160412⟩

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