Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYnote-240: A Randomized, Double-Blind, Phase III Trial
Journal
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Journal Volume
38
Journal Issue
3
Pages
193-202
Date Issued
2020
Author(s)
Finn R.S.
Ryoo B.-Y.
Merle P.
Kudo M.
Bouattour M.
Lim H.Y.
Breder V.
Edeline J.
Chao Y.
Ogasawara S.
Yau T.
Garrido M.
Chan S.L.
Knox J.
Daniele B.
Ebbinghaus S.W.
Chen E.
Siegel A.B.
Zhu A.X.
KEYnote-240 investigators
Abstract
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.
SDGs
Other Subjects
immunological antineoplastic agent; monoclonal antibody; pembrolizumab; adolescent; adult; aged; clinical trial; controlled study; double blind procedure; female; human; liver cell carcinoma; liver tumor; male; middle aged; phase 3 clinical trial; randomized controlled trial; very elderly; young adult; Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Carcinoma, Hepatocellular; Double-Blind Method; Female; Humans; Liver Neoplasms; Male; Middle Aged; Progression-Free Survival; Young Adult
Publisher
NLM (Medline)
Type
journal article