Immunotherapy Could Signal a 'Change in the Treatment Paradigm' For Patients with HCC

HIMALAYA trial investigators who are currently testing the combination of (the immunotherapies) tremelimumab and Imfinzi (durvalumab) in patients with inoperable, advanced hepatocellular carcinoma (HCC), or liver cancer, say that positive phase 2 results could signal a “change in the treatment paradigm” for the disease — but further study is needed in phase 3 trials.

In an interview with OncLive, CURE’s sister publication, Dr. Bruno Sangro, of the Clínica Universidad de Navarra School of Medicine in Pamplona, Spain, discussed the importance of finding more potent and well-tolerated therapies in this disease space, and why immunotherapy drugs like the ones being investigated in the HIMALAYA trial are vital in this mission.

According to Sangro: “The wider the spectrum of choices, the better we will be able to treat our patients.”

OncLive: How could positive results from the HIMALAYA study impact the treatment paradigm for advanced HCC?

Sangro: We know that the combination of (the immunotherapy) atezolizumab (Tecentriq) and (the antiangiogenic) bevacizumab (Avastin) is better than (the kinase inhibitor) sorafenib in terms of prolonging survival in patients with advanced HCC that are naïve to systemic therapies. But, there is still room for improvement.

With the activity that we have seen with this combination of tremelimumab and Imfinzi, a 30% response rate and prolonged survival in the cohort of patients treated, I think it compares well with the preliminary activity we did see with the combination of atezolizumab and bevacizumab.

If the HIMALAYA trial is positive, it may provide an alternative regimen that is absent of an antiangiogenic agent. What we need in the HCC field is more different combinations that are active. I don’t believe we should neglect the activity of any of the combinations that are currently being tested in phase 3 trials, including the combination of tremelimumab and durvalumab. Also, this includes combinations with TKIs (tyrosine kinase inhibitors), such as the combination of lenvatinib and (the immunotherapy) pembrolizumab (Keytruda).

The more combinations we have, the better, because we will have to adapt our treatments to the patients in terms of comorbidities and other circumstances that may make us able to tailor the choice of the activity to the profile of the patient.

What is your take-home message regarding this study?

We are witnessing a change in the treatment paradigm for HCC. It is clear that immunotherapy is in the HCC arena to stay, and that we have to build on the activity of (these) PD-1/PD-L1 inhibitors to increase treatment efficacy, while preserving tolerability, to provide a spectrum of different active combination therapies, but not neglecting the possibility that patients may still benefit from single-agent immunotherapy. We should not forget that our patients are often elderly and frequently have different comorbidities. The wider the spectrum of choices, the better we will be able to treat our patients.