Phase 3 RATIONALE-301 Study Evaluates Tislelizumab vs Sorafenib in HCC


Ghassan K. Abou-Alfa, MD, discusses the phase 3 RATIONALE-301 trial of frontline tislelizumab vs sorafenib in patients with hepatocellular carcinoma.

Ghassan K. Abou-Alfa, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the phase 3 RATIONALE-301 trial (NCT03412773) which evaluated frontline tislelizumab vs sorafenib (Nexavar) in patients with hepatocellular carcinoma (HCC).

In the RATIONALE-301 trial, tislelizumab demonstrated improved health-related quality of life, physical functioning, fatigue, and HCC symptom index when compared with sorafenib. However, the agent did not reduce pain significantly vs sorafenib.

According to Alfa, the findings from this study, as well as those from a phase 3 study (NCT03764293) and the phase 3 LEAP-002 study (NCT03713593), highlight the question as to what the role is of single-agent, anti-PD-1 in regard to HCC.


0:10 | The third study was another intriguing point for all of us. This is another anti-PD-1, tislelizumab, vs sorafenib in an inferiority study looking for equivalency between the 2, which is fair and an appropriate question as we have seen from other alternative studies like nivolumab [Opdivo] vs sorafenib, pembrolizumab [Keytruda] vs placebo, and recently, the HIMALAYA study [NCT03298451] of durvalumab [Imfinzi] single-agent vs sorafenib, which was looked at also for inferiority. Intriguingly, that study was positive, because it did not show any non-inferiority and it showed a clear non-separation between the 2 arms of the study, bringing up an important point in regard to what is the role of single-agent, anti-PD-1 in regard to HCC.

1:07 | These are great results, but we have to build the story together. Interestingly, it appears to be that they're not all equal in regard to either single-agent or combination therapies. Number 2, we're getting a sense that some of them are probably better than others. Of course, number 3 is that the dynamics in the field are evolving so fast that even comparisons among studies is not correct, not necessarily fair. On top of this, we now have the combination of camrelizumab [SHR-1210] and rivoceranib [Apatinib] with again, 22 months vs sorafenib. Also, we have the lenvatinib [Lenvima] plus pembrolizumab, which again is a negative study, but close to 22 months as well.

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