{"doi":"10.1158/2767-9764.c.6719612.v2","title":"Data from Salvage Ipilimumab plus Nivolumab after Anti-PD-1/PD-L1 Therapy in Advanced Hepatocellular Carcinoma","abstract":"<div><p>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%, <i>n</i> = 16), other anti-VEGF plus anti-PD-(L)1 combinations (31%, <i>n</i> = 10), and anti-PD-(L)1 monotherapy (19%, <i>n</i> = 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.</p>Significance:<p>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.</p></div>","journal":null,"year":2023,"id":409670,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9277,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1042539,"name":"Mir Lim","orcid":"0000-0002-6102-0887","position":1,"is_corresponding":false},{"id":339300,"name":"Chester Kao","orcid":"0000-0003-2568-2071","position":2,"is_corresponding":false},{"id":613641,"name":"Daniel Shu","orcid":null,"position":3,"is_corresponding":false},{"id":106840,"name":"Amit G. Singal","orcid":"0000-0002-1172-3971","position":4,"is_corresponding":false},{"id":288342,"name":"Anne M. Noonan","orcid":"0000-0001-8083-8492","position":5,"is_corresponding":false},{"id":1043302,"name":"Paige Griffith","orcid":null,"position":6,"is_corresponding":false},{"id":936970,"name":"Marina Baretti","orcid":"0000-0003-0125-2405","position":7,"is_corresponding":false},{"id":317428,"name":"Won Jin Ho","orcid":"0000-0003-2644-5086","position":8,"is_corresponding":false},{"id":363754,"name":"Ihab R. Kamel","orcid":"0000-0003-0511-7796","position":9,"is_corresponding":false},{"id":277002,"name":"Mark Yarchoan","orcid":"0000-0003-4401-0748","position":10,"is_corresponding":false},{"id":326809,"name":"David Hsiehchen","orcid":"0000-0001-9139-302X","position":11,"is_corresponding":false},{"id":1042538,"name":"Stephanie Alden","orcid":"0000-0003-0500-8696","position":0,"is_corresponding":true}],"reference_count":20,"raw_metadata":null,"created_at":"2026-07-19T01:21:27.199694Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}