Immune checkpoint inhibitor (ICI)-based regimens (atezolizumab+bevacizumab, durvalumab+tremelimumab, nivolumab+ipilimumab) are now a first-line standard for advanced hepatocellular carcinoma (HCC). For Child-Pugh (CP) A patients, regorafenib, cabozantinib, and ramucirumab are approved second-line agents, but there is no approved second-line systemic therapy for CP-B. In CP-B historical controls treated with best supportive care, median progression free survival (PFS) was \~1.4 months in a REACH trial subgroup analysis and \~1.9 months in a CELESTIAL trial subgroup analysis. Regorafenib demonstrated benefit as a post-sorafenib second-line therapy in CP-A patients in the RESORCE trial, but prospective evidence in CP-B is lacking. A multicenter retrospective study of CP-B patients receiving second-line regorafenib after sorafenib reported a median PFS of 1.8 months, and prospective data after ICI-based first-line therapy are not available.
This study will evaluate the efficacy and safety of regorafenib as second-line therapy in CP-B patients with disease progression after first-line ICI-based treatment. The primary objective is to demonstrate superiority over historical controls, with PFS as the primary endpoint.
After written informed consent, all participants will receive regorafenib. Regorafenib will be administered at 120 mg orally once daily at the same time each day, after a meal with water, for 3 consecutive weeks followed by 1 week off (4-week cycle). Treatment must start within 3 days after screening and will continue until disease progression, unacceptable toxicity, withdrawal of consent, or study termination, whichever occurs first. After treatment discontinuation, patients will be followed every 12 week (+/-7 days) for survival status and subsequent anticancer therapies, and survival follow-up will continue for at least 12 months after enrollment of the last participant.