Atezolizumab plus Bevacizumab versus Sorafenib for Unresectable Hepatocellular Carcinoma: Results from Older Adults Enrolled in the IMbrave150 Randomized Clinical Trial.

The efficacy of systemic first-line treatments in older adults with unresectable hepatocellular carcinoma (HCC) has not been well-studied. We compared the safety and efficacy of atezolizumab plus bevacizumab versus sorafenib as a first-line treatment in younger versus older patients with unresectable HCC. This global, phase 3, open-label, randomized clinical trial (IMbrave150) recruited patients aged ≥18 years with locally advanced metastatic or unresectable HCC, an Eastern Cooperative Oncology Group performance status score of 0 or 1, and Child-Pugh class A liver function who had not previously received systemic therapy for liver cancer. Patients received either 1,200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks or 400 mg sorafenib orally twice daily until loss of clinical benefit or unacceptable toxicity. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary outcomes were the incidence of adverse events and time to deterioration of patient-reported outcomes (PROs). This subgroup analysis evaluated safety and efficacy endpoints in patients <65 years, ≥65 to <75 years, and ≥75 years. Of 501 patients, 165 patients were randomized to sorafenib and 336 were randomized to atezolizumab plus bevacizumab (175 patients <65 years; 106 patients ≥65 to <75 years; 55 patients ≥75 years). Across all age groups, patients receiving atezolizumab plus bevacizumab had longer median OS (<65: 18.0 vs. 12.2 months [HR, 0.57; 95% CI: 0.40-0.82]; ≥65 to <75: 19.4 vs. 14.9 months [HR, 0.80; 95% CI: 0.52-1.23]; ≥75: 24.0 vs. 18.0 months [HR, 0.72, 95% CI: 0.37-1.41]) and PFS than those receiving sorafenib. Time to deterioration for multiple PROs was delayed for patients receiving atezolizumab plus bevacizumab, including older adults. There were no clinically meaningful differences in toxicity between age groups. Atezolizumab plus bevacizumab is safe and effective in adults <65, ≥65 to <75, and ≥75. Treatment was well-tolerated even in elderly patients.

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Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.

Déclaration de conflit d'intérêts

Dr. Daneng Li reports research funding to his institution from AstraZeneca and Brooklyn ImmunoTherapeutics. He serves as a consultant and has received honoraria from Adagene, Advanced Accelerator Applications, Bayer Healthcare, Coherus BioSciences, Eisai, Exelixis, Genentech, Ipsen Biopharmaceuticals, Lexicon Pharmaceuticals, Merck, MiNA Therapeutics, QED Therapeutics, Servier, Sun Pharma, Taiho Pharmaceutical, and TerSera Therapeutics. Dr. Han Chong Toh has received research funding from Bristol Myers Squibb, Merck, and Bayer Healthcare; honoraria from Roche, Merck, and Eisai; and consultancy fee from Tessa Therapeutics Ltd. Dr. Philippe Merle has received advisory board fees from Bayer Healthcare, Bristol Myers Squibb, Eisai, Eli Lilly and Company, Ipsen Biopharmaceuticals, Merck, and Roche. Dr. Kaoru Tsuchiya has received lecture fees from Eisai, Chugai Pharmaceutical, and Eli Lilly. Dr. Sairy Hernandez is employed by Genentech USA. Dr. Wendy Verret was employed by Genentech USA at the time the analysis was completed. Dr. Alan Nicholas is employed by Genentech USA. Dr. Masatoshi Kudo has received grant support from AbbVie, Dainippon Sumitomo Pharma, Gilead Sciences, Otsuka Pharmaceutical, Taiho Pharmaceutical, and Takeda Medical Research Foundation; grant support and consulting fees from Bayer and Merck; grant support, lecture fees, and consulting fees from Bristol Myers Squibb and Eisai; consulting fees from Chugai Pharmaceutical and Ono Pharmaceutical; and is the Editor-in-Chief of Liver Cancer. No other potential conflict of interest relevant to this article was reported.