Outcomes of Sequential Immune Checkpoint Inhibitor Retreatment After Atezolizumab Plus Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma.

[BACKGROUND AND AIM] Data on sequential immune checkpoint inhibitor (ICI) retreatment following initial atezolizumab plus bevacizumab (Atez + Bev) are limited. This study aimed to evaluate the efficacy and safety of sequential ICI retreatment in patients with unresectable hepatocellular carcinoma (uHCC).

[METHODS] Of 835 patients with uHCC treated with Atez + Bev, 75 who underwent ICI retreatment after initial Atez + Bev therapy were included in this multicenter retrospective study that assessed the efficacy and safety of ICIs.

[RESULTS] The participants received one of three sequential retreatments with ICI regimens: durvalumab plus tremelimumab (n = 58), retreatment with Atez + Bev (n = 15), and durvalumab monotherapy (n = 2). The objective response rates (ORRs)/disease control rates (DCRs) for the initial Atez + Bev and sequential ICI retreatment were 34.7%/89.3% and 18.7%/54.7%, respectively. No significant differences in antitumor response were observed among the three ICI retreatment regimens. Patients who achieved a good antitumor response (≥ stable disease) following retreatment showed a significantly longer overall survival. Multivariate analysis identified prior objective response to Atez + Bev as an independent predictor of disease control after retreatment (odds ratio: 3.79, p = 0.016). Immune-related adverse events (irAEs) requiring corticosteroids occurred in 26.7% of the patients during ICI retreatment, with enterocolitis and rash being the most common. The recurrence rate of irAEs was 15.4% in patients with previous steroid-requiring irAEs.

[CONCLUSIONS] Sequential ICI retreatment may be a viable therapeutic option for selected patients with uHCC, particularly those with a favorable response to prior Atez + Bev. Although less effective than first-line therapy, careful patient selection and monitoring ensure efficacy with acceptable safety.