IO and VEGF Inhibition in Hepatocellular Carcinoma

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Richard S. Finn, MD: I don’t think the TKIs [tyrosine kinase inhibitors] are going away front line. Even though we’re learning about a lot of exciting data with immuno-oncology [IO] agents, a lot of the evolving data are in combination with TKIs. Recently, we saw the approval of bevacizumab and atezolizumab in advanced liver cancer. And this, I think, is a real game-changer. Tony, can you give us your insights into that new data set?

Tanios S. Bekaii-Saab, MD, FACP: Thank you, Rich. Certainly, the landscape is changing, and changing very rapidly. As you said, I still remember the days even before sorafenib, there were absolutely no options other than doxorubicin and toying with tamoxifen and Megace. Today, we have so many options. It got quite confusing for a while, with a lot of first-line and second-line options and a lot of fast-track approvals. It made the landscape a little bit confusing and complex, good and bad. And then come the data with IMbrave150 with atezolizumab and bevacizumab. We’ve had some disappointments with nivolumab versus sorafenib, which did not pan out. And there was a whole question about are we on the right track with immune therapies and whether we should move forward, move away, find subsets. So, it got even more complex, and a little bit of disappointment until we saw these data, which do consolidate the importance now of moving into dual IO combinations, whether non-IO plus IO, VEGF plus IO, or IO plus IO. But focusing on the atezolizumab and bevacizumab, it made a lot of sense to add a VEGF inhibitor to a PD-1 or a PD-L1 inhibitor.

VEGF plays a role in immunosuppression; blocking VEGF seems to essentially reverse some of that immunosuppression, primarily promoting T-cell infiltration into the tumor. That enhances the activity of these PD-1, PD-L1 inhibitors, and that would set the stage for IMbrave150 with atezolizumab plus bevacizumab versus sorafenib, which was a phase 3 trial that was first reported out at the ESMO Asia Congress, with an update on PROs [patient-reported outcomes] at ASCO GI This was a study that had 336 patients with 2 co-primary end points, including overall survival and progression-free survival . And response rate as a secondary end point, PROs and the quality-of-life measures, etc. The study hit every one of those points with a positive mark. Improvement in survival, improvement in progression-free survival, although the median progression-free survival was not as impressive, it’s the hazard ratio, that 30% of patients who seemed to derive the most benefit, with a hazard ratio of 0.59.

Interestingly, as expected, the toxicities were mostly hypertension in the atezolizumab/bevacizumab. And sorafenib is exactly where you expect it to be, with hand-and-foot syndrome, fatigue, and others. It’s quite a challenging drug. But most importantly, when looking at patient-reported outcomes, quality of life, and overall noxious toxicities, atezolizumab/bevacizumab essentially wins on every one of those points. So, you get better survival, better PFS, better response rate, better quality of life, PRO, better toxicity profile. You win on every point, and it brings back this flavor of immuno-oncology into the first line. I think that is a game changer. That changes how we treat patients in the first line for HCC, I’d say for most patients. It can’t be for all patients. There are certain caveats. But for, I’d say, 80%, 90% of our patients, that’s going to be the standard.

Transcript Edited for Clarity