Tislelizumab is noninferior to sorafenib for first-line treatment of patients with unresectable hepatocellular carcinoma (HCC), according to research presented at ESMO Congress 2022.

Tislelizumab prolonged the median overall survival (OS) by nearly 2 months in the final analysis of the phase 3 RATIONALE-301 study. This improvement met statistical significance for noninferiority to sorafenib, but the significance threshold for superiority was not met.

“Single-agent tislelizumab demonstrated a clinically meaningful benefit vs sorafenib, with a favorable and manageable safety profile in this patient setting,” said study author Masatoshi Kudo, MD, PhD, of Kindai University in Osaka, Japan.

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For this study (ClinicalTrials.gov Identifier: NCT03412773), Dr Kudo and colleagues enrolled patients who had unresectable HCC that was naïve to systemic therapy. Patients had 1 or more measurable lesions and an ECOG performance status of 0-1.

Patients were randomly assigned to receive tislelizumab (n=342) or sorafenib (n=332). Tislelizumab was given at 200 mg every 3 weeks, and sorafenib was given at 400 mg orally twice per day. Patients were treated until disease progression or intolerable toxicity. 

At baseline, the median ages were 62.0 years (range, 25.0-86.0) in the tislelizumab arm and 60.0 years (range, 23.0-86.0) in the sorafenib arm. Most patients were men (84.5% and 84.6%, respectively), had HBV infection (59.4% and 62.0%), and had extrahepatic spread (64.0% and 59.6%).

At a minimum follow-up of 33.0 months, 6.7% of patients in the tislelizumab arm and 0.9% in the sorafenib arm remained on study treatment. 

The study’s primary endpoint was OS. Tislelizumab achieved noninferiority but did not reach the threshold for superiority (P <.0223) against sorafenib. The median OS was 15.9 months in the tislelizumab arm and 14.1 months in the sorafenib arm (stratified hazard ratio [sHR], 0.85; 95% CI, 0.712-1.019; P =.0398). 

At 12 months, the OS rate was 58.3% in the tislelizumab arm and 57.2% in the sorafenib arm. At 36 months, the OS rate was 29.2% and 20.3%, respectively. 

The overall response rate was 14.3% in the tislelizumab arm and 5.4% in the sorafenib arm. The complete response rate was 2.9% and 0.3%, respectively. The median duration of response was 36.1 months in the tislelizumab arm and 11.0 months in the sorafenib arm. 

The median progression-free survival (PFS) was 2.1 months in the tislelizumab arm and 3.4 months in the sorafenib arm (sHR, 1.11; 95% CI, 0.92-1.33). At 24 months, the PFS rate was 13.9% and 6.1%, respectively. 

Grade 3 or higher treatment-related adverse events (AEs) were reported in 22.2% of patients in the tislelizumab arm and in 53.4% of patients in the sorafenib arm. Immune-mediated AEs occurred in 17.2% and 3.1%, respectively. 

Fatal treatment-related AEs occurred in 3 patients in the tislelizumab arm and 2 in the sorafenib arm. 

Disclosures: This research was supported by BeiGene, Ltd. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Qin S, Kudo M, Meyer T, et al. Final analysis of RATIONALE-301: Randomized, phase III study of tislelizumab versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma. Presented at ESMO 2022; September 9-13, 2022. Abstract LBA36.