Nivolumab and ipilimumab as second or later line therapy in hepatocellular carcinoma: A retrospective study.

Abstract

e16167 Background: Despite advances in first-line for systemic therapy in hepatocellular carcinoma (HCC), tumor progression remains common. However, the efficacy and safety of nivolumab plus ipilimumab (NIVO+IPI) as second or later line treatment in HCC remains limited. Methods: We retrospectively reviewed consecutive HCC patients who received NIVO (1mg/kg) and IPI (3mg/kg) every 3 weeks as later-line between Oct 2020 and Jun 2025. Endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAEs). Results: A total of 49 patients (Barcelona Clinic Liver Cancer stage B/C: 15/34) were included. Median age was 53 years (range 24–68). And 24, 14, and 11 patients received NIVO+IPI regimen as 2-, 3-, and 4-line therapy, respectively. Prior systemic regimens included PD-1/PD-L1 inhibitor plus anti-VEGF (38.8%), PD-1 inhibitor plus tyrosine kinase inhibitor (TKI, 42.9%), TKI alone (10.2%), PD-1 inhibitor alone (6.1%) or dual immunotherapy (2.0%). All patients had received prior local treatments. Median number of treatment cycles was 2 (range: 1-20). Among 32 evaluable patients, ORR was 12.5% (4/32) for the whole cohort, including 6.3% (2/32) complete response (CR), with 11.8% (2/17), 20% (2/10) and 0% (0/5) for 2-L, 3-L, and 4-L patients, respectively. And DCR was 56.3% (18/32) for the whole cohort, with 58.8% (10/17), 50% (5/10) and 60% (3/5) for 2-L, 3-L, and 4-L patients, respectively. With a median follow-up of 12 months, median PFS was 2.1 months (95% CI 2.0–4.2); the median duration of response was 3.4 months. The median OS was not reached, and 6, 12-month OS rates were 96.4% (95% CI 89.8%-100%) and 84.4% (95% CI 64.3%-100%). TRAEs of any grade occurred in 36.8% (18/49) and grade 3–4 TRAEs in 20.4% (10/49). The most common immune-related events were hepatitis (8.2%) and dermatitis (6.1%). Treatment discontinuation due to toxicity occurred in 4.1% (2/49), and no treatment-related deaths were observed. Conclusions: In this real-world cohort of HCC progressing on systemic and local therapies, NIVO+IPI demonstrated clinically meaningful efficacy and manageable toxicity as later line therapy. These data support NIVO+IPI as a viable salvage treatment option in the later line setting and warrant prospective evaluation.