The treatment landscape for unresectable hepatocellular carcinoma (HCC) has undergone significant evolution with the emergence of immunotherapy-based combination therapies, according to Dr. Aparna Parikh, Associate Professor of Medicine at Harvard Medical School and physician at Massachusetts General Hospital.
The field now offers two FDA-approved first-line immunotherapy combinations for patients with Child-Pugh A unresectable HCC: atezolizumab plus bevacizumab, and durvalumab plus tremelimumab. These approvals represent a paradigm shift in how the disease is treated.
Treatment Selection Considerations
With no head-to-head trials comparing these combinations, treatment selection relies heavily on patient-specific factors. Dr. Parikh notes that while atezolizumab plus bevacizumab remains the more commonly prescribed regimen, careful consideration of bleeding risk is essential.
"The challenging thing with bevacizumab is that there is a risk of bleeding," Dr. Parikh explains. "This is especially prevalent in patients that have untreated or active varices, or have not had a chance to get an endoscopy." For such patients, durvalumab plus tremelimumab may be more appropriate.
Emerging Combination Under Evaluation
The combination of durvalumab plus lenvatinib has also been studied in this setting. While this regimen offers an oral treatment option through lenvatinib, Dr. Parikh questions its positioning in the current treatment algorithm.
"It's hard to think of a scenario where a patient would be eligible for durvalumab plus lenvatinib without being eligible for either atezolizumab plus bevacizumab or durvalumab plus tremelimumab," she observes. Additionally, lenvatinib carries its own distinct adverse effect profile that requires consideration.
Clinical Implementation
The patient population studied across these combinations remains relatively consistent, focusing on those with Child-Pugh A liver function status and good performance status. This overlap in eligible patient populations, combined with the established safety and efficacy profiles of current first-line options, may limit the practical utility of durvalumab plus lenvatinib in the first-line setting.
Treatment decisions ultimately require careful evaluation of individual patient characteristics, including liver function, bleeding risk, and the presence of varices, to determine the most appropriate immunotherapy-based combination.
