Rechallenge of Atezolizumab Plus Bevacizumab Therapy in Patients With Unresectable Hepatocellular Carcinoma

Background: Atezolizumab plus bevacizumab (AB) is a standard first-line therapy for unresectable hepatocellular carcinoma (HCC). However, data on the efficacy and safety of AB rechallenge (re-AB) after discontinuation are limited. Methods: We conducted a retrospective analysis of 13 patients with unresectable HCC who received initial AB treatment and re-AB at the University of Yamanashi and Fujita Health University. Rechallenge was defined as reinitiating AB after prior discontinuation followed by one or more other systemic therapies. Tumor responses were assessed using RECIST v1.1 and modified RECIST (mRECIST), and adverse events (AEs) were evaluated according to CTCAE v5.0. Results: During initial AB, the objective response rate (ORR), disease control rate (DCR), and median progression-free survival (mPFS) were 15%, 69%, and 3.7 months, respectively. AB was discontinued due to disease progression or immune-related AEs. Re-AB was administered after a median of two intervening regimens. In the re-AB phase, ORR, DCR, and mPFS were 15%, 54%, and 4.7 months, respectively. Despite prior progression, two patients achieved partial response and five had stable disease. No worsening of previously observed AEs occurred during re-AB. Conclusions: AB rechallenge may be a safe and potentially effective treatment option for selected patients with unresectable HCC, even after discontinuation due to disease progression or adverse events.