Richard S. Finn, MD, on Hepatocellular Carcinoma: Recent Data on Lenvatinib Plus Pembrolizumab
ESMO Congress 2022
Richard S. Finn, MD, of the Geffen School of Medicine at the University of California, Los Angeles, discusses primary phase III results from the LEAP-002 study of pembrolizumab, an anti–PD-1 therapy, plus lenvatinib, the orally available multiple receptor tyrosine kinase inhibitor, vs lenvatinib monotherapy in patients with advanced hepatocellular carcinoma (Abstract LBA34).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
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.
Jean-Pascal Machiels, MD, PhD, of Belgium’s Cliniques universitaires Saint-Luc (UCLouvain), discusses the primary results of the phase III KEYNOTE-412 study of pembrolizumab plus chemoradiation therapy (CRT) vs placebo plus CRT for patients with locally advanced head and neck squamous cell carcinoma (Abstract LBA5).
Marleen Kok, MD, PhD, of The Netherlands Cancer Institute in Amsterdam, discusses the initial results from the BELLINI trial, which tested whether short-term preoperative nivolumab, either as monotherapy or in combination with low-dose doxorubicin or novel immunotherapy combinations, can induce immune activation in patients with early-stage triple-negative breast cancer with tumor-infiltrating lymphocytes (Abstract LBA13).
Georgina V. Long, MD, PhD, of the Melanoma Institute Australia, discusses results from the CheckMate 915 trial, an analysis of the pretreatment circulating tumor DNA, along with other clinical and translational baseline factors, and their association with disease recurrence in patients with stage IIIB–D/IV melanoma treated with adjuvant immunotherapy (Abstract 788O).
Charles Swanton, PhD, of The Francis Crick Institute, discusses a newly discovered mechanism of action for air pollution–induced non–small cell lung cancer in which particles linked to climate change appear to promote cancerous changes. The finding might pave the way for new potential approaches to lung cancer prevention and treatment (Abstract LBA1).
Jonathan E. Rosenberg, MD, of Memorial Sloan Kettering Cancer Center, discusses recent findings on the safety and antitumor activity of enfortumab vedotin-ejfv given intravenously as monotherapy or in combination with pembrolizumab to previously untreated cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer (Abstract LBA73).