ARTICLE ABSTRACT
Combination anti-PD-(L)1/CTLA-4 blockade is approved in patients with hepatocellular carcinoma (HCC) in the first-line setting or after sorafenib, but whether this treatment has efficacy after prior anti-PD-(L)1 therapy is unknown. We performed a multicenter retrospective review of patients with advanced HCC treated with ipilimumab plus nivolumab after prior anti-PD-(L)1 therapy, excluding patients with prior anti-CTLA-4 treatment. Of the 32 patients who met our inclusion criteria, prior anti-PD-(L)1 regimens included atezolizumab plus bevacizumab (50%, n=16), other anti-VEGF plus anti-PD-(L)1 combinations (31%, n=10), and anti-PD-(L)1 monotherapy (19%, n=6). The median number of prior systemic therapies was two (range 1-8). The objective response rate (ORR) with ipilimumab plus nivolumab by RECIST 1.1 was 22% (1 CR (3%), 6 PR (19%), 8 SD (25%), 16 PD (50%), and 1 NE (3%)), and objective response was associated with improved PFS and OS. Immune related adverse events were reported in 13 patients (41%), with no new safety signals. This study demonstrates that ipilimumab plus nivolumab has efficacy in patients with HCC who have received prior anti-PD-(L)1 therapy, suggesting that failure to respond to prior PD-(L)1 blockade should not preclude treatment with salvage ipilimumab plus nivolumab. Prospective studies are needed to define the optimal sequence of therapies.
