Outcome and management of patients with hepatocellular carcinoma who achieved complete response to immunotherapy-based systemic therapy

Background & Aims: The outcome of patients with hepatocellular carcinoma (HCC) who achieved complete response (CR) to immune-checkpoint-inhibitor (ICI)-based systemic therapies is unclear. Approach & Results: Retrospective study of patients with HCC who had CR according to mRECIST to ICI-based systemic therapies from 28 centers in Asia, Europe, and the United States. Of 3933 patients with HCC treated with ICI-based non-curative systemic therapies, 174 (4.4%) achieved CR according to mRECIST (CR-mRECIST) and 97 (2.5%) had CR according to RECISTv1.1 (CR-RECISTv1.1) as well. The mean age of the total cohort (male, 85%; BCLC-C, 70%) was 65.9±9.8 years. The majority (83%) received ICI-based combination therapies. Median follow-up was 32.2 (95%CI, 29.9-34.4) months. One- and 3-year overall survival (OS) rates were 98% and 86%. One- and 3-year recurrence-free survival (RFS) rates were excellent in patients with CR-mRECIST-only and CR-RECISTv1.1 (78% and 55%; 70% and 42%). Among patients who discontinued ICIs for reasons other than recurrence, those who received immunotherapy for ≥6 months after first mRECIST CR had a longer RFS than those who discontinued immunotherapy earlier ( p =0.008). Of 9 patients who underwent curative surgical conversion therapy, 8 (89%) had pathological CR (CR-RECISTv1.1, n= 2/2; CR-mRECIST-only, n= 6/7). Conclusion: OS and RFS of patients with CR-mRECIST-only and CR-RECISTv1.1 were excellent, and 6 of 7 patients with CR-mRECIST-only who underwent surgical conversion therapy had pathological CR. Despite potential limitations, these findings support the use of mRECIST in the context of immunotherapy for clinical decision-making. When considering ICI discontinuation, treatment for at least 6 months beyond CR seems advisable.