Tislelizumab vs Sorafenib as First-Line Treatment for Unresectable Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, and additional first-line treatments are needed. The programmed cell death protein 1 inhibitor tislelizumab demonstrated efficacy and a tolerable safety profile as second-line HCC treatment.

To investigate efficacy and safety of tislelizumab vs sorafenib tosylate for first-line treatment of unresectable HCC. Design, Setting, and Participants: The open-label, global, multiregional phase 3 RATIONALE-301 randomized clinical trial enrolled systemic therapy-naive adults with histologically confirmed HCC, Barcelona Clinic Liver Cancer stage B or C disease, disease progression following (or patient was not amenable to) locoregional therapy, Eastern Cooperative Oncology Group performance status of 1 or less, and Child-Pugh class A, between December 27, 2017, and October 2, 2019. Data cutoff was July 11, 2022. Intervention: Patients were randomized 1:1 to receive tislelizumab, 200 mg intravenously every 3 weeks, or sorafenib tosylate, 400 mg orally twice daily. Main Outcomes and Measures: The primary end point was overall survival (OS); secondary end points included objective response rate, progression-free survival, duration of response, and safety.