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.ANN-LII CHENGKEYnote-240 investigators2021-08-312021-08-3120201527-7755https://www.scopus.com/inward/record.uri?eid=2-s2.0-85077942597&doi=10.1200%2fJCO.19.01307&partnerID=40&md5=1179f56ba3aac953bdea882a25d0b0bfhttps://scholars.lib.ntu.edu.tw/handle/123456789/580037PURPOSE: 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]SDG3immunological 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 Adultjournal article10.1200/JCO.19.01307317903442-s2.0-85077942597