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

Autor:	Finn RS; University of California, Los Angeles, Los Angeles, CA., Ryoo BY; Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea., Merle P; Lyon North Hospital, Lyon, France., Kudo M; Kindai University Faculty of Medicine, Osaka, Japan., Bouattour M; Beaujon University Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France., Lim HY; Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea., Breder V; NN Blokhin National Medical Research Center of Oncology, Ministry of Health, Moscow, Russian Federation., Edeline J; Centre Eugène Marquis, Rennes, France., Chao Y; Taipei Veterans General Hospital, Taipei, Taiwan., Ogasawara S; Chiba University Graduate School of Medicine, Chiba, Japan., Yau T; The University at Hong Kong, Hong Kong, People's Republic of China., Garrido M; Pontificia Universidad Catolica de Chile, Santiago, Chile., Chan SL; State Key Laboratory of Translation Oncology, Sir YK Pao Centre for Cancer, The Chinese University of Hong Kong, Hong Kong, People's Republic of China., Knox J; Princess Margaret Cancer Centre and University of Toronto, Toronto, Ontario, Canada., Daniele B; Ospedale del Mare, Napoli, Italy., Ebbinghaus SW; Merck, Kenilworth, NJ., Chen E; Merck, Kenilworth, NJ., Siegel AB; Merck, Kenilworth, NJ., Zhu AX; Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA., Cheng AL; National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2020 Jan 20; Vol. 38 (3), pp. 193-202. Date of Electronic Publication: 2019 Dec 02.
DOI:	10.1200/JCO.19.01307
Abstrakt:	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.
Databáze:	MEDLINE
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