Nivolumab in patients with advanced hepatocellular carcinoma and Child-Pugh class B cirrhosis: Safety and clinical outcomes in a retrospective case series.

Background: Nivolumab demonstrated durable responses and safety in patients with hepatocellular carcinoma (HCC) with Child-Pugh class A cirrhosis in the CheckMate 040 trial, with rates of hepatotoxicity that were similar to those of non-HCC populations. To the authors' knowledge, the safety and efficacy of nivolumab has not been established in patients with Child-Pugh class B (CPB) cirrhosis, a population with limited therapeutic options and a poor prognosis.

Methods: The authors conducted a retrospective case series of patients with advanced HCC and CPB cirrhosis who were treated with nivolumab and enrolled in the University of California at San Francisco Hepatobiliary Tissue Bank and Registry. Safety endpoints included rates of grade ≥3 adverse events (AEs) (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.03]) and serious AEs, immune-related AEs (irAE), steroid requirement, and discontinuation. Efficacy endpoints included time on treatment, the objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, overall survival, and progression-free survival.

Results: A total of 18 patients were included, with 72% of them (13 of 18 patients) previously treated with sorafenib. The majority of patients (94%; 17 of 18 patients) experienced a grade ≥3 AE, with treatment-related grade ≥3 AEs reported in 28% of patients (5 of 18 patients). irAEs were reported to occur in approximately 50% of patients (9 of 18 patients), and 28% (5 of 18 patients) required steroids. Treatment-related AEs required discontinuation in 4 patients (22%). The median time on treatment was 2.3 months (95% CI, 1.9 months to upper bound not estimable). The objective response rate was 17% (3 of 18 patients), including 2 partial responses and 1 complete response. The median overall survival from the time of nivolumab initiation was 5.9 months (95% CI, 3 months to upper bound not estimable), with a median progression-free survival of 1.6 months (95% CI, 1.4-3.5 months).

Conclusions: Patients with CPB HCC experienced high rates of AEs, although the frequency of irAEs was similar to that of patients with Child-Pugh class A HCC in the CheckMate 040 trial. A subset of patients experienced prolonged tumor responses. Nivolumab warrants further study in patients with CPB HCC.