Emerging Updates in Front-Line Immunotherapy for Unresectable Hepatocellular Carcinoma (uHCC)

James J. Harding, MD, provides a high-level overview of systemic therapy for untreated unresectable hepatocellular carcinoma (uHCC) based on NCCN Guidelines, and discusses the evolving treatment landscape, including the rationale for combination immunotherapy (IO) and how additional IO combinations may address unmet needs like depth of response and resistance.

James J. Harding, MD, reviews the ongoing phase 3 CheckMate 9DW trial, which is investigating nivolumab plus ipilimumab (NIVO + IPI) vs lenvatinib or sorafenib as first-line (1L) treatment for unresectable hepatocellular carcinoma (uHCC).

James J. Harding, MD, discusses the primary (overall survival [OS]) and secondary end points (overall response rate [ORR], duration of response [DOR]) of the CheckMate 9DW trial, and explores how the inclusion of the lenvatinib (LEN) arm informs the treatment landscape, as well as the safety profiles of first-line systemic immunotherapy in patients with uHCC, focusing on the most significant adverse events seen with nivolumab plus ipilimumab (NIVO + IPI).

James J. Harding, MD, compares the responses observed with nivolumab plus ipilimumab (NIVO + IPI) therapy in the CheckMate 9DW trial to other first-line (1L) immunotherapy (IO) regimens for unresectable hepatocellular carcinoma (uHCC), including the HIMALAYA 5-year update (STRIDE) and the IMbrave150 trial (atezolizumab [ATEZO] + bevacizumab [BEV]), highlighting differences in efficacy and treatment outcomes.

James J. Harding, MD, discusses how the initial findings from CheckMate 9DW inform the role of nivolumab plus ipilimumab (NIVO + IPI) in the first-line (1L) treatment landscape for unresectable hepatocellular carcinoma (uHCC), considering factors such as efficacy, safety, and patient characteristics (eg, age) when selecting between first-line systemic immunotherapy (IO) regimens.

James J. Harding, MD, discusses the remaining unmet needs in the first-line (1L) treatment space for unresectable hepatocellular carcinoma (uHCC) and how 1L immunotherapy (IO) combinations like nivolumab plus ipilimumab (NIVO + IPI) may help address these gaps, while highlighting unanswered questions and offering clinical pearls for managing uHCC.