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

Daneng Li; Han Chong Toh; Philippe Merle; Kaoru Tsuchiya; Sairy Hernandez; Wendy Verret; Alan Nicholas; Masatoshi Kudo

doi:10.1159/000525671

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

Liver Cancer. 2022 Jul 13;11(6):558-571. doi: 10.1159/000525671. eCollection 2022 Dec.

Authors

Daneng Li¹, Han Chong Toh², Philippe Merle³, Kaoru Tsuchiya⁴, Sairy Hernandez⁵, Wendy Verret⁵, Alan Nicholas⁵, Masatoshi Kudo⁶

Affiliations

¹ Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, California, USA.
² National Cancer Centre Singapore, Singapore, Singapore.
³ Department of Gastroenterology and Hepatology, Croix-Rousse University Hospital, Lyon, France.
⁴ Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
⁵ Genentech, Inc, South San Francisco, California, USA.
⁶ Faculty of Medicine, Kindai University, Osaka, Japan.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: Atezolizumab plus bevacizumab is safe and effective in adults <65, ≥65 to <75, and ≥75. Treatment was well-tolerated even in elderly patients.

Keywords: Atezolizumab; Bevacizumab; Hepatocellular carcinoma; Older adults.

Grants and funding

This study was funded by F. Hoffmann-La Roche/Genentech. The study was designed and data analyzed by the sponsor in collaboration with the investigators. Editorial support was provided by Thea Gray of Health Interactions and funded by the sponsor.