• N. Engl. J. Med. · May 2020

    Randomized Controlled Trial Multicenter Study

    Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma.

    • Richard S Finn, Shukui Qin, Masafumi Ikeda, Peter R Galle, Michel Ducreux, Tae-You Kim, Masatoshi Kudo, Valeriy Breder, Philippe Merle, Ahmed O Kaseb, Daneng Li, Wendy Verret, Derek-Zhen Xu, Sairy Hernandez, Juan Liu, Chen Huang, Sohail Mulla, Yulei Wang, Ho Yeong Lim, Andrew X Zhu, Ann-Lii Cheng, and IMbrave150 Investigators.
    • From the Jonsson Comprehensive Cancer Center, Geffen School of Medicine at UCLA, Los Angeles (R.S.F.), the City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte (D.L.), and Genentech, South San Francisco (W.V., S.H., Y.W.) - all in California; the People's Liberation Army Cancer Center, Jinling Hospital, Nanjing (S.Q.), and Roche Product Development (D.-Z.X., J.L., C.H.) and Jiahui International Cancer Center, Jiahui Health (A.X.Z.), Shanghai - all in China; National Cancer Center Hospital East, Kashiwa (M.I.), and Kindai University Faculty of Medicine, Osaka (M.K.) - both in Japan; University Medical Center Mainz, Mainz, Germany (P.R.G.); Gustave Roussy Cancer Center, Paris-Saclay University, Villejuif (M.D.), and University Hospital La Croix-Rousse, Lyon (P.M.) - both in France; Seoul National University College of Medicine (T.-Y.K.) and Samsung Medical Center, Sungkyunkwan University School of Medicine (H.Y.L.) - both in Seoul, South Korea; N.N. Blokhin Russian Cancer Research Center, Moscow (V.B.); the University of Texas M.D. Anderson Cancer Center, Houston (A.O.K.); Hoffmann-La Roche, Mississauga, ON, Canada (S.M.); Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston (A.X.Z.); and the National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei (A.-L.C.).
    • N. Engl. J. Med. 2020 May 14; 382 (20): 1894-1905.

    BackgroundThe combination of atezolizumab and bevacizumab showed encouraging antitumor activity and safety in a phase 1b trial involving patients with unresectable hepatocellular carcinoma.MethodsIn a global, open-label, phase 3 trial, patients with unresectable hepatocellular carcinoma who had not previously received systemic treatment were randomly assigned in a 2:1 ratio to receive either atezolizumab plus bevacizumab or sorafenib until unacceptable toxic effects occurred or there was a loss of clinical benefit. The coprimary end points were overall survival and progression-free survival in the intention-to-treat population, as assessed at an independent review facility according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1).ResultsThe intention-to-treat population included 336 patients in the atezolizumab-bevacizumab group and 165 patients in the sorafenib group. At the time of the primary analysis (August 29, 2019), the hazard ratio for death with atezolizumab-bevacizumab as compared with sorafenib was 0.58 (95% confidence interval [CI], 0.42 to 0.79; P<0.001). Overall survival at 12 months was 67.2% (95% CI, 61.3 to 73.1) with atezolizumab-bevacizumab and 54.6% (95% CI, 45.2 to 64.0) with sorafenib. Median progression-free survival was 6.8 months (95% CI, 5.7 to 8.3) and 4.3 months (95% CI, 4.0 to 5.6) in the respective groups (hazard ratio for disease progression or death, 0.59; 95% CI, 0.47 to 0.76; P<0.001). Grade 3 or 4 adverse events occurred in 56.5% of 329 patients who received at least one dose of atezolizumab-bevacizumab and in 55.1% of 156 patients who received at least one dose of sorafenib. Grade 3 or 4 hypertension occurred in 15.2% of patients in the atezolizumab-bevacizumab group; however, other high-grade toxic effects were infrequent.ConclusionsIn patients with unresectable hepatocellular carcinoma, atezolizumab combined with bevacizumab resulted in better overall and progression-free survival outcomes than sorafenib. (Funded by F. Hoffmann-La Roche/Genentech; ClinicalTrials.gov number, NCT03434379.).Copyright © 2020 Massachusetts Medical Society.

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