Richard S. Finn, MD, on Hepatocellular Carcinoma: Recent Data on Lenvatinib Plus Pembrolizumab

The LEAP-002 study was a large phase three double blind placebo controlled study in advanced liver cancer in the frontline setting, evaluating the combination of Lenvatinib and Pembrolizumab versus Lenvatinib alone. This study was based on earlier data, a single arm phase one B study in the frontline setting with both these drugs, which showed very interesting activity. A 36% objective response rate, as well as a survival of over 21 months, which in the first line setting of liver cancer was a signal to pursue this definitive study. Lenvatinib has already approved in the front line setting in the United States and Pembrolizumab has accelerated approval in the second line setting. So in this study, we demonstrated that the overall survival with the combination was over 21 months, which was expected. However, the control arm performed much better than we expected. That is to say Lenvatinib had a survival of about 19 months in this population. If we look at historical data with Lenvatinib, from the REFLECT study, the pivotal study that got it approved, overall survival was about 13 and a half months. So unfortunately, the study did not meet its primary endpoint of overall survival. There was a dual primary endpoint of PFS, and again, at the primary analysis for PFS, there was no significant difference between the two arms. We did see that with longer follow up that there was a tail to the curve for Len Pembro, looking at the two year benchmark about 16% of patients did not progress with a combination, whereas 9% on single agent Lenvatinib did not progress. When we look at objective responses, the objective response rate with the combination was 25% in line with what we saw in the phase one B and Lenvatinib had a response rate of about 17 and half percent, which was in line with what was expected with single agent Lenvatinib. When we look at safety, there were really no new safety signals. The safety profile looked like single agent Lenvatinib, no added toxicity with Pembrolizumab, but at the end of the day, the study did not meet its end point. We did establish that the combination does prolong a long survival in advanced liver cancer and specifically Lenvatinib as a single agent in advanced liver cancer provided a survival of 19 months, which is really a reminder that this drug plays an important role in our patients with advanced liver cancer, even in this modern age of new combinations that are being evaluated and being approved.