Emerging Combination Therapies for HCC


Ruth He, MD, discusses potential options for physicians in their treatment of unresectable hepatocellular carcinoma.

Ruth He, MD: Multiple clinical trials are ongoing to evaluate the combination of immune checkpoint inhibitors, VEGF inhibitors, and tyrosine kinase inhibitors [TKIs] in the treatment of advanced HCC [hepatocellular carcinoma]. Based on the phase 1b study of lenvatinib plus pembrolizumab, there was a reported response rate of 36% and a prolonged duration of response. Based on the early promising data, this regimen has been looked at in a phase 3 study, LEAP-002. We’re waiting for the results of that study.

Other combinations, such as cabozantinib and atezolizumab, are being evaluated in the COSMIC-312 study, while the phase 3 study is ongoing and we’re waiting for a readout of that study. There are also combinations of immune checkpoint inhibitors, such as I/O–I/O [immuno-oncology] combinations being evaluated. Moreover, there are the CTLA4 combinations with checkpoint inhibitors. Nivolumab and ipilimumab have accelerated approval in the second-line setting, as the combination is being evaluated vs sorafenib or lenvatinib in the frontline setting of CheckMate 9DW.

There are also I/O–I/O combinations being evaluated, such as the CTLA4 combinations with immune checkpoint inhibitors. The nivolumab-ipilimumab combination has accelerated approval in the second-line setting as a combination and is now being evaluated in the frontline setting in comparison with sorafenib or lenvatinib. The HIMALAYA study is looking at the combination of tremelimumab and durvalumab vs sorafenib. The study has completed accrual, and we are waiting for events. Overall, we will have to wait for phase 3 studies to know how to integrate these new regimens into our treatment paradigm.

Transcript edited for clarity.

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