Gholam Explores the Phase 3 RATIONALE-301 Study of Sorafenib in HCC


Pierre Gholam, MD, discusses the phase 3 RATIONALE-301 study of frontline tislelizumab vs sorafenib for patients with hepatocellular carcinoma.

Pierre Gholam, MD, professor at Case Western Reserve University School of Medicine in Cleveland, Ohio, discusses the phase 3 RATIONALE-301 (NCT03412773) study of frontline tislelizumab (BGB-A317) vs sorafenib (Nexavar) for patients with hepatocellular carcinoma (HCC).

The global, phase 3 RATIONALE-301 trial randomized 674 patients to receive tislelizumab, an IgG4 anti-PD-1 monoclonal antibody, or sorafenib, a tyrosine kinase inhibitor. Enrollment was open to patients with treatment-naive HCC who had a Child-Pugh class A, an ECOG performance status of 0 or 1, and no tumor thrombus involving main the trunk of portal vein, inferior vena cava, or clinical evidence of portal hypertension with bleeding varices at screening.

According to Gholam, efficacy results of the study showed noninferiority of tislelizumab compared with sorafenib for overall survival and objective response rate. There were also improvements in tolerability demonstrated.


0:10 | This study was the comparison of frontline tislelizumab, which is another IgG4 anti-PD-1 monoclonal antibody, to sorafenib. The first-line study aimed to see whether this new agent was non-inferior to sorafenib with the possibility of testing for superiority of the data.

0:37 | This study ultimately showed that tislelizumab achieved the 15.9-month median overall survival in the first-line compared with 14.1 months in the sorafenib arm. There were some subset analyses which suggested that tislelizumab may have some differential efficacy in patients older than 65 years, potentially patients with more advanced disease in terms of tumor spread, perhaps patients with hepatitis C infection, and female patients. There was otherwise not a lot of difference in terms of adverse event profile between the 2 arms.

1:27 | Notably, the progression-free survival was oddly longer for sorafenib at 3.6 months than for a tislelizumab at 2.2 months, a somewhat peculiar finding that I think has yet to be explained. Overall, there were fewer discontinuations and those modifications with tislelizumab as compared [with] sorafenib. If one looked at adverse events leading to death, they were comparable between the 2 arms.

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