Updates in Frontline Treatment of Metastatic Liver Cancer - Episode 3

IMbrave150 Trial: Frontline Treatment of Advanced HCC

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Richard S. Finn, MD: Rich, you’re a medical oncologist at Moffitt Cancer Center, so you’re a great person to comment on some of the new data in liver cancer. I’ve been very blessed and fortunate to be involved with the IMbrave150 study. Could you go over some of that data and its impact in the past month since its approval?

Richard Kim, MD: The treatment of advanced HCC (hepatocellular carcinoma) for medical oncologists have come a long way. As you know, many years ago, the only drug that was available for the TKI (tyrosine kinase inhibitor) was sorafenib. Since then, we’ve made some progress with lenvatinib. Recently, you were part of the IMbrave150, a large phase 3 study comparing ATEZO (atezolizumab) plus bevacizumab with sorafenib as standard of care.

The rationale is that single checkpoint inhibitors, such as nivolumab or Keytruda (pembrolizumab), they have a single-agent activity as well, anywhere from 20% to 50% as single agent, even though the phase 3 data never really panned out. You may recall that, in the past, bevacizumab also has been studied as a single agent as well, with the response rate hovering for a multi-phase 2 study around 10% to 12%. The rationale for combining bevacizumab is that you actually reduce the VEGF immunosuppression, and, thus, allow promoting of the T-cell infiltration to the tumor. Basically, change the microenvironment for possible immunotherapy to work better.

The IMbrave150 was a randomized phase 3 study, 2-to-1 randomization, comparing the study arm, which was ATEZO (atezolizumab) plus bevacizumab versus sorafenib. It had a co-primary endpoint with progression-free survival and overall survival. The outcome was very positive. There was not only improvement in response rate but the combination, which hovered a little over 30%, and there was improvement in PFS (progression-free survival). A median OS (overall survival) the last time it was presented was not reached in the combination arm compared with sorafenib. This was one of the first trials out there in the first-line setting that showed a benefit over a TKI of sorafenib.

Based on these data, I think the NCCN (National Comprehensive Cancer Network) changed its first-line guidelines to include the combination of ATEZO (atezolizumab) plus BEV (bevacizumab). Based on the trial, it is superior to sorafenib. Therefore, now in our practice and in other institutions as well, this is the combination of a choice in a patient who’s the right fit. When I say ‘right fit,’ these are patients with Child-Pugh A who do not have any history or a variceal bleeding history. The key point here is that, in the study that we participate in as well, all the patients must have an EGD (esophagogastroduodenoscopy) done and have the varices banded before they went on to the study, which we don’t typically do. In the right patient population, the combination of ATEZO (atezolizumab) plus BEV (bevacizumab) is the new standard treatment for advanced HCC.

Richard S. Finn, MD: This is really a hallmark study in that it’s the first time sorafenib has been beat. You alluded to the data from the REFLECT study, which was lenvatinib versus sorafenib, a positive study but positive for noninferiority. The overall survival endpoints were not statistically significant in that study, but lenvatinib did improve PFS and response rates.

IMbrave150, though, takes that to a different level; we have response rates now of 27%, and the median duration hasn’t been reached. Survival has a hazard ratio of 0.58 versus an active control, which no study today has, but it’s not because of lack of trying. No study today has shown that survival data, as well as PFS; hazard ratios are 0.59.

Transcript Edited for Clarity