Dr Iglesia on Unmet Needs in Second-Line Therapy Selection in HCC

Michael Iglesia, MD, PhD, instructor, John T. Milliken Department of Medicine, Division of Oncology, Washington University School of Medicine, discusses unmet needs and uncertainties surrounding second-line therapy considerations in hepatocellular carcinoma (HCC).

There is a need for more robust data to guide treatment decisions in second-line HCC, Iglesia begins. Patients often transition to second-line therapy following progression on initial regimens such as durvalumab (Imfinzi) plus tremelimumab (Imjudo) or bevacizumab (Avastin) plus atezolizumab (Tecentriq), he details. Iglesia shares that in his own practice, he typically favors agents like cabozantinib and other TKIs in the second line, often bypassing sorafenib (Nexavar) and lenvatinib (Lenvima). However, there is a lack of evidence to support one approach over the other, he emphasizes.

Of the limited clinical data available, insights can be derived from trials such as phase 3 CELESTIAL trial (NCT01908426) evaluating cabozantinib (Cabometyx) vs placebo in patients with HCC who were previously exposed to sorafenib, Iglesia states. The trial demonstrated an overall survival benefit with cabozantinib vs placebo. Notably, many patients on the trial had previously received a VEGF-targeting TKI or immune checkpoint inhibitor, Iglesia says. This trial population could be considered comparable to the group of patients who had received what we think of as modern first-line therapy, he adds.

Significant gaps persist in determining optimal second-line treatment following initial checkpoint inhibitor or combination therapies, Iglesia continues. Questions have also risen regarding the use of lenvatinib vs approved agents in the second line following progression on either the phase 3 HIMALAYA (NCT0329845) or IMbrave150 (NCT03434379) regimens, he says. Additionally, some patients who previously received an immune checkpoint inhibitor may benefit more from switching to alternate first-line therapies such as bevacizumab plus atezolizumab, Iglesia states. Addressing these uncertainties requires well-designed trials aimed at elucidating the comparative effectiveness and safety of different treatment sequences in advanced HCC, Iglesia concludes.