Evaluating Two Rechallenge Strategies of Immune Checkpoint Inhibitors: Durvalumab Plus Tremelimumab in Advanced Hepatocellular Carcinoma

AIM:This study aimed to evaluate the safety and efficacy of durvalumab plus tremelimumab in patients with advanced hepatocellular carcinoma who have previously received atezolizumab plus bevacizumab (Atez/Bev). Additionally, it seeks to assess the feasibility of administering immunotherapy after the occurrence of immune-mediated adverse events (imAEs) in real-world clinical practice. METHODS:This retrospective study analyzed data from patients with advanced hepatocellular carcinoma treated with durvalumab plus tremelimumab at four Japanese institutions. Clinical outcomes, adverse events, tumor dynamics, and serum cytokine and chemokine levels were evaluated, with a focus on efficacy following prior Atez/Bev treatment. RESULTS:Durvalumab plus tremelimumab was administered to 68 patients. The objective response rate was 10.3%, and the disease control rate was 58.8%. Median progression-free survival was 3.1 months (95% confidence interval 2.0-4.9). imAEs occurred in 50.0% of patients, with colitis being the most common (22.1%). Durvalumab was safely readministered to 14 patients after imAE resolution, although five experienced recurrence. Among 33 patients (48.5%) previously treated with Atez/Bev, improved responses were noted, including two partial responses. Tumor growth dynamics decreased in 60.0% of patients receiving sequential therapy. Common adverse events included elevated liver enzymes (aspartate aminotransferase 50.0%, alanine aminotransferase 48.5%), pruritus (45.6%), and rash (44.1%). CONCLUSIONS:Durvalumab plus tremelimumab therapy is feasible with proper imAE management and patient selection. Sequential treatment following Atez/Bev offers clinical benefit in advanced hepatocellular carcinoma, although some may experience rapid progression. Further biomarker research is needed to optimize immunotherapy strategies.