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RATIONALE-301: Final Analysis Shows Benefit of Tislelizumab in Hepatocellular Carcinoma

By: Celeste L. Dixon
Posted: Wednesday, October 12, 2022

Tislelizumab is an effective and safe first-line treatment option for patients with unresectable hepatocellular carcinoma, Masatoshi Kudo, MD, PhD, of Kindai University, Osaka, Japan, and colleagues reported during the European Society for Medical Oncology (ESMO) Congress 2022 (Abstract LBA36). Their global, phase III, randomized trial—RATIONALE-301—matched the anti–PD-1 monoclonal antibody against sorafenib, with a primary endpoint of overall survival noninferiority. In fact, with a minimum study follow-up of 33 months at data cutoff, tislelizumab showed a “clinically meaningful” overall survival benefit, with a median overall survival of 15.9 months versus 14.1 months with sorafenib.

In addition, this final analysis of RATIONALE-301 demonstrated a higher overall response rate for tislelizumab versus sorafenib (14.3% vs. 5.4%), more durable responses (median duration of response, 36.1 vs. 11.0 months), and longer median treatment duration (4.1 vs. 2.7 months). However, median progression-free survival with tislelizumab was 2.2 months versus 3.6 months with sorafenib.

The 674 participating patients were randomly assigned on a 1:1 basis to treatment. All were systemic therapy–naive adults with histologically confirmed hepatocellular carcinoma, Barcelona Clinic Liver Cancer stage B/C, and Child-Pugh class A; they were not amenable to or had experienced disease progression after locoregional therapy. They received tislelizumab intravenously at 200 mg every 3 weeks or sorafenib orally at 400 mg twice daily until disease progression, intolerable toxicity, withdrawal, or cessation of benefit.

Safety, a secondary endpoint, was deemed acceptable, with profiles for both agents consistent with previous data. Rates of grade 3 or higher adverse events (48.2% vs. 65.4%) and adverse events leading to discontinuation of treatment (10.9% vs. 18.5%) “were lower with tislelizumab compared with sorafenib, [and] adverse events leading to death were [considered] low across both treatments,” Dr. Kudo and co-investigators noted. Immune-mediated adverse events (hepatitis and hypothyroidism) were reported in 5% or more of tislelizumab-treated patients.

Disclosure: The study authors’ disclosure information can be found at

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