Salvage Ipilimumab plus Nivolumab after Anti-PD-1/PD-L1 Therapy in Advanced Hepatocellular Carcinoma

• Published in: Cancer research communications Vol. 3; no. 7; pp. 1312 - 1317
• Main Authors: Alden, Stephanie L, Lim, Mir, Kao, Chester, Shu, Daniel, Singal, Amit G, Noonan, Anne, Griffith, Paige, Baretti, Marina, Ho, Won Jin, Kamel, Ihab, Yarchoan, Mark, Hsiehchen, David
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 01-07-2023
• Subjects: B7-H1 Antigen; Carcinoma, Hepatocellular - chemically induced; Clinical-Stage Research; Gastrointestinal Cancers; Humans; Immunotherapy; Ipilimumab; Liver Neoplasms - chemically induced; Nivolumab
• ISSN: 2767-9764; 2767-9764
• DOI: 10.1158/2767-9764.CRC-23-0072

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%,
= 16), other anti-VEGF plus anti-PD-(L)1 combinations (31%,
= 10), and anti-PD-(L)1 monotherapy (19%,
= 6). The median number of prior systemic therapies was 2 (range, 1-8). The objective response rate with ipilimumab plus nivolumab by RECIST 1.1 was 22% [1 complete response (3%), 6 partial response (19%), 8 stable disease (25%), 16 progressive disease (50%), and 1 not evaluable (NE) (3%)], and objective response was associated with improved progression-free survival and overall survival. 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.
Anti-PD-(L)1 containing regimens are the preferred first-line treatment for advanced HCC, but whether salvage with PD-(L)1/CTLA-4 blockade is effective in patients who have failed prior anti-PD-(L)1 therapy is unknown. Our study demonstrates that ipilimumab plus nivolumab has clinical activity in patients with advanced HCC previously treated with anti-PD-(L)1 therapy, supporting the continued use of this regimen in the late-line setting after prior anti-PD-(L)1 exposure.