Tislelizumab demonstrates non-inferior OS compared to sorafenib for treating hepatocellular carcinoma

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Published: 26 Sep 2022
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Prof Masatoshi Kudo - Kindai University Faculty of Medicine, Osaka, Japan

Prof Masatoshi Kudo speaks to ecancer about the final analysis of RATIONALE-301 trial.

The study was designed to compare the efficacy and safety of tislelizumab versus sorafenib as a first-line systemic treatment in participants with unresectable hepatocellular carcinoma (HCC).

Prof Kudo explores the substudy which investigated the safety, tolerability, PK, and preliminary efficacy in HCC in Japanese participants.

Currently there is no single agent checkpoint inhibitor approved by a phase III study for HCC or liver cancer. Currently the immunotherapy approved for HCC is atezolizumab plus bevacizumab only, so PD-1 antibodies, or PD-L1 antibodies, alone has not been approved. So this study, the RATIONALE-301, tested the efficacy and safety of tislelizumab, a PD-L1 antibody and sorafenib. The primary endpoint was OS.

What was the methodology behind the study?

The methodology, this is an open-label randomised controlled trial, an international, multicentre, multiregional global study.

What were your findings?

The trial design was, first, try to show the non-inferiority, OS non-inferiority, to sorafenib and then if non-inferiority was proved then we would attempt to test the superiority to sorafenib. Our finding was OS non-inferiority was shown: the median OS of tislelizumab was 15.9 months, the median OS of sorafenib was 14.1 months, a hazard ratio of 0.85 and a 95% confidence interval, the upper limit of 95% CI was 1.019 which was lower than the upper limit of the pre-specified 95% CI of 1.08. So this study met its primary endpoint of non-inferiority but could not show superiority.

Another finding – response rate was also better in tislelizumab, 14.3% versus 5.4%. Adverse events, in terms of adverse events the safety profile was consistent with previous reports and also severe treatment related or treatment emergent adverse events were also less frequent than with sorafenib. The duration of response was very long – 36.1 months in tislelizumab, which is the longest as compared with previous immunotherapy [inaudible].

Anything else to add?

Tislelizumab had a favourable safety profile and an easily manageable safety profile compared with sorafenib and the grade 3 or more treatment emergent AEs leading to discontinuation or interruption were fewer than with sorafenib. So the safety profile is very good and the most important thing, as already said, the duration of response is very long – 36 months. That is the most important point of this study.