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Sangro Says Immunotherapy May Be the Future of HCC Treatment

Kelly Davio
Published: Sunday, Sep 16, 2018

Bruno Sangro, MD
Bruno Sangro, MD
Although treatment for patients with hepatocellular carcinoma (HCC) has advanced in recent years, the disease remains a challenging one to treat.

However, research trends now point to immune checkpoint inhibitors alone and in combination as a promising new direction research in HCC, explained Bruno Sangro, MD. The key will be determining which patients will be likely to benefit from this class of agents, he added.

In a presentation during the 12th International Liver Cancer Association (ILCA) Annual Conference, held in London, United Kingdom, Sangro, director of the liver unit and codirector of the hepatobiliary oncology area at Clínica Universidad de Navarra in Pamplona, Spain, discussed immunotherapy and immune-based biomarkers in liver cancer.

Immunotherapy has already entered the landscape. In September 2017, the FDA granted an accelerated approval to nivolumab (Opdivo) for the treatment of patients with HCC following prior sorafenib (Nexavar), regardless of PD-L1 status.

The approval is based on 154 patients enrolled in the phase I/II CheckMate-040 trial, in which the overall response rate by blinded independent central review was 18.2% per mRECIST criteria for those who had previously been treated with sorafenib. Now, the community is eagerly awaiting the results of the phase III CheckMate-459 trial (NCT02576509), which is comparing nivolumab with sorafenib in the frontline setting for patients with advanced HCC. Additionally, the randomized, multicenter, phase III HIMALAYA trial (NCT03298451) is looking at 4 treatment arms for patients with previously untreated, unresectable HCC with 2 regimens of durvalumab (Imfinzi) plus tremelimumab, durvalumab monotherapy, and sorafenib alone.

In an interview with OncLive, Sangro discussed the current landscape for systemic therapies, new directions with immunotherapy, and the need for greater research into combination therapies for HCC.

OncLive: Please provide an overview of your presentation on immunotherapy and immune-based biomarkers in HCC.

Sangro: What we know is that, if you treat patients at the most advanced stages of the disease after sorafenib, the results in single-arm trials show that¬—compared with the behavior you would expect from placebo-treated patients—immunotherapy-treated patients survive much longer. That was the basis on which the FDA and other regulatory agencies worldwide have accepted nivolumab, which is an anti–PD-1 therapy, for the treatment of patients with advanced-stage HCC in the second-line setting.

Based on those results and the data we earlier produced with another anti–CTLA-4 inhibitor, tremelimumab, [which showed] in a much smaller trial that there was some activity there, the field has evolved to large phase III trials. [The results] in the first- and second-line settings for advanced disease have been challenging the standard of care, which is sorafenib for the first-line setting and best supportive care for the second-line setting. We are awaiting the results of these trials, which will be hopefully less than 1 year from now.

Eventually, this will change the treatment paradigm if these studies are positive. Even if they’re not, the knowledge of the activity of these agents in liver cancer has promoted the clinical development of combinations of immunotherapies and agents that we already know are active, such as sorafenib, lenvatinib (Lenvima), cabozantinib (Cabometyx), regorafenib (Stivarga), or ramucirumab (Cyramza).

The early things we know about some of these combinations are that they may be highly active. This has changed the whole spectrum of clinical development pathways. Now immunotherapy is not only tested in combination with the advanced patients, they are also tested as adjuvant therapies in those who have been resected or treated with percutaneous ablation and have a high chance of having recurrent disease, as they have different factors of poor prognosis.

Immunotherapy is now challenging the whole spectrum of stages in patients with HCC. The issue is, we know that there is fraction of patients who respond very well, and these patients survive for a very long time. However, there is also a fraction of patients who seem to have no effect at all, and others in which the effect is difficult to illustrate or capture. Now, with 4 or 5 different drugs soon to be available, there is an absolute need to have markers that could identify patients who would benefit most from one therapy or another.

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