Immune Checkpoint Inhibitor Rechallenge in Unresectable Hepatocellular Carcinoma: A Multicenter Efficacy and Safety...

Area of Science:

• Hepatobiliary Cancers
• Medical Oncology
• Immunotherapy

Background:

• Immune checkpoint inhibitors (ICIs) are standard for unresectable hepatocellular carcinoma (HCC).
• Discontinuation of ICIs due to resistance or adverse events necessitates alternative strategies.
• ICI rechallenge is an option for patients with unresectable HCC requiring treatment cessation.

Purpose of the Study:

• To investigate the efficacy and safety of immune checkpoint inhibitor (ICI) rechallenge in patients with unresectable hepatocellular carcinoma (HCC).
• To evaluate outcomes, including event-free survival and objective response, after resuming ICI therapy.
• To assess the incidence and severity of immune-related adverse events during ICI rechallenge.

Main Methods:

• Retrospective analysis of 272 patients with unresectable HCC treated with ICIs between March 2019 and May 2024.
• Patients initially received ICIs, discontinued due to resistance or severe adverse events, and were subsequently rechallenged.
• Outcomes assessed included event-free survival, objective response, disease control (RECIST 1.1), and immune-related adverse events (irAEs) for both first-line (ICI-1) and second-line (ICI-2) therapies.

Main Results:

• Median event-free survival was 5.3 months for ICI-1 and 4.4 months for ICI-2.
• Objective response rates were 23.2% for ICI-1 and 18.4% for ICI-2; disease control rates were 69.9% and 48.2%, respectively.
• Grade 3-4 immune-related adverse events occurred in 18.4% during ICI-1 and 19.9% during ICI-2, with no treatment-related deaths.

Conclusions:

• Immune checkpoint inhibitor (ICI) rechallenge can be a beneficial strategy for patients with unresectable hepatocellular carcinoma (HCC) who discontinued initial therapy.
• Rechallenging with ICIs demonstrates potential for improved prognosis in select HCC patients without significant additional safety concerns.
• This approach offers a viable option for managing unresectable HCC when first-line ICI treatment is not sustainable.