Post Conference Perspectives: Immunotherapy Combinations for Unresectable HCC - Episode 6

IMbrave150 in Unresectable HCC


Richard S. Finn, MD: The IMbrave150 study is the first phase III study to read out on 1 of these combination strategies—in this case, a PD-L1 [programmed death-ligand 1] inhibitor, atezolizumab, with a VEGF-targeted agent, bevacizumab. This phase III study is of significance because it’s the first time we have a phase III study that hasn’t beaten sorafenib. There have been numerous studies that have aimed at improving survival for patients in the frontline of a cancer space. All those have been negative. We did have a positive phase III study with lenvatinib, but that was a noninferiority end point.

Now we have a combination that has shown that we have improved survival in this population. The study was presented at the ESMO [European Society for Medical Oncology] Asia [Congress] 2019 meeting. This study was a fairly common design for a phase III study in liver cancer. Patients had advanced liver cancer, defined as Barcelona [Clinic Liver Cancer] stage C, or Barcelona B, who are intermediate patients who progressed on locoregional treatments. Patients had to be Child-Pugh class A, with a performance status of 0 or 1. Also, it’s important, because we’re using bevacizumab, that if patients had to have an endoscopy within 6 months of gong on study, those were controlled.

This study grew out of a larger phase I/II experience that showed that response rates with this combination were in the 30% range, which was very high for liver cancer. And the study was a global study. The baseline characteristics of the patients were pretty common for a global type of liver cancer study, so they were very similar to what we’ve seen in other studies with sorafenib. And the study met both its primary end points of improving progression-free survival as well as improving overall survival.

For overall survival, the hazard ratio is 0.58. Sorafenib had a survival of about 13.2 months. The survival in the treatment of atezolizumab and bevacizumab still has not been reached at the time of this analysis. This study point has a median follow-up of about 8.5 months, and the study met its end points at the first interim analysis, so the study was stopped. The study did confirm the data from the phase I/II study, in that the response rate in the phase III study was 27%, which again is very high for the liver cancer population. We know that sorafenib has improved survival, and many of the other drugs approved have improved survival but without inducing significant durable responses. What we’re seeing here are very durable, deep responses with the combination when they do occur. And finally, we’re seeing this translate into a survival benefit.

Not only did the study meet its primary end points, as well as secondary end point of response rate, but the combination was very well tolerated. Overall, adverse events were very similar compared with sorafenib. But if we look at drug-related adverse events, they were actually higher in the control arm, in the sorafenib arm, than in the combination arm. Keep in mind this was a selected population. These patients had to have an endoscopy and varices controlled before coming on study. But overall, if we look at patient-reported outcomes that were presented at the ESMO Asia meeting, there was a significant delay in deterioration of patients’ quality of life in the combination arm versus sorafenib.

I think many of us in the liver cancer space view this as a practice-changing study. Obviously, it does not have a regulatory approval yet, but the fact that for the first time in more than a decade we have something that has beaten sorafenib—this will be a very good option for patients. We can now tell patients that we have a regimen that is safe and more effective than what we’ve had in the past.

Transcript Edited for Clarity