{"doi":"10.1016/s0140-6736(25)01720-9","title":"Perioperative camrelizumab plus rivoceranib versus surgery alone in patients with resectable hepatocellular carcinoma at intermediate or high risk of recurrence (CARES-009): a randomised phase 2/3 trial","abstract":null,"journal":"The Lancet","year":2025,"id":632955,"datarank":0.5897738449086489,"base_score":3.9318256327243257,"endowment":3.9318256327243257,"self_citation_contribution":0.5897738449086489,"citation_network_contribution":0.0,"self_endowment_contribution":0.5897738449086489,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":50,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":912337,"name":"Jia Fan","orcid":"0009-0009-5318-0256","position":1,"is_corresponding":false},{"id":1640871,"name":"Shaolai Zhou","orcid":null,"position":2,"is_corresponding":false},{"id":1640872,"name":"Yunfan Sun","orcid":null,"position":3,"is_corresponding":false},{"id":1640874,"name":"Fei Liang","orcid":null,"position":4,"is_corresponding":false},{"id":570917,"name":"Yuan Ji","orcid":"0000-0002-9151-8192","position":5,"is_corresponding":false},{"id":1640877,"name":"Fangming Gu","orcid":null,"position":6,"is_corresponding":false},{"id":348973,"name":"Tao Li","orcid":"0000-0003-0792-003X","position":7,"is_corresponding":false},{"id":806919,"name":"Li Peng","orcid":"0000-0001-5594-3506","position":8,"is_corresponding":false},{"id":7627,"name":"Tao Peng","orcid":"0000-0001-5260-7128","position":9,"is_corresponding":false},{"id":1640878,"name":"Xiaolun Huang","orcid":null,"position":10,"is_corresponding":false},{"id":88514,"name":"Zhenbin Ding","orcid":null,"position":11,"is_corresponding":false},{"id":1640879,"name":"Dousheng Bai","orcid":null,"position":12,"is_corresponding":false},{"id":1613656,"name":"Bangde Xiang","orcid":null,"position":13,"is_corresponding":false},{"id":1640881,"name":"Guang Tan","orcid":null,"position":14,"is_corresponding":false},{"id":1640883,"name":"Tianfu Wen","orcid":null,"position":15,"is_corresponding":false},{"id":1535245,"name":"Yongyi Zeng","orcid":null,"position":16,"is_corresponding":false},{"id":1253840,"name":"Feng Han","orcid":"0000-0002-0274-9272","position":17,"is_corresponding":false},{"id":831198,"name":"Yu Zhang","orcid":"0000-0001-5969-2388","position":18,"is_corresponding":false},{"id":1640890,"name":"Shengdong Wu","orcid":null,"position":19,"is_corresponding":false},{"id":1139294,"name":"Haitao Zhao","orcid":"0000-0002-1415-2617","position":20,"is_corresponding":false},{"id":1046524,"name":"Yi Chen","orcid":"0009-0009-2594-7608","position":21,"is_corresponding":false},{"id":1640893,"name":"Guoming Shi","orcid":null,"position":22,"is_corresponding":false},{"id":1640894,"name":"Zhiguo Hou","orcid":null,"position":23,"is_corresponding":false},{"id":311461,"name":"Ying Sun","orcid":"0000-0002-3027-7727","position":24,"is_corresponding":false},{"id":12200,"name":"Wenqing Zhu","orcid":"0000-0001-8229-0934","position":25,"is_corresponding":false},{"id":88515,"name":"Jian Zhou","orcid":"0000-0002-9917-5622","position":26,"is_corresponding":false},{"id":268819,"name":"Zheng Wang","orcid":"0000-0001-7138-8581","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Perioperative camrelizumab plus rivoceranib versus surgery alone in patients with resectable hepatocellular carcinoma at intermediate or high risk of recurrence (CARES-009): a randomised phase 2/3 trial","abstract":"<h4>Background</h4>Surgical resection is the preferred curative approach for patients with early-stage hepatocellular carcinoma, but recurrence remains a major challenge. Consequently, neoadjuvant and adjuvant therapies have been proposed to reduce tumour burden and mitigate the risk of recurrence. The CARES-009 trial aimed to evaluate perioperative camrelizumab plus rivoceranib in patients with resectable hepatocellular carcinoma at intermediate or high risk of recurrence.<h4>Methods</h4>This multicentre, open-label, randomised, phase 2/3 trial enrolled patients with hepatocellular carcinoma classified as China Liver Cancer Staging (CNLC) stage Ib-IIIa without Vp4 portal vein tumour thrombosis (corresponding to Barcelona Clinic Liver Cancer stage A with tumour >5 cm, stage B, or stage C without Vp4 involvement or extrahepatic metastasis) at 16 hospitals in China. Patients were randomly assigned (1:1) to receive perioperative therapy or surgery alone and were stratified by CNLC stage and hepatitis B virus (HBV) infection status. The perioperative group received two cycles of neoadjuvant camrelizumab plus rivoceranib, followed by surgery and adjuvant camrelizumab plus rivoceranib. The primary endpoint was event-free survival (EFS) and was assessed by investigators (who were not masked to group assignment) in the intention-to-treat population. Safety was evaluated in the as-treated population. This trial is registered with ClinicalTrials.gov (NCT04521153) and is ongoing.<h4>Findings</h4>Between March 25, 2021, and Jan 29, 2024, 294 patients (87% male; 99% Han Chinese) were randomly assigned to the perioperative group (n=148) or surgery alone group (n=146). At a prespecified interim analysis, with a median follow-up of 21·3 months, median EFS was 42·1 months (95% CI 23·2-not estimable [NE]) in the perioperative group versus 19·4 months (14·9-NE) in the surgery alone group (hazard ratio 0·59, 95% CI 0·41-0·85; p=0·0040). Grade 3 or worse treatment-related adverse events occurred in 53 (38%) patients in the perioperative group and no patients in the surgery alone group. Two treatment-related deaths occurred during neoadjuvant therapy in the perioperative group: one due to hepatic failure, assessed as possibly related to treatment, and one due to combined hepatic and renal failure, with the causality deemed indeterminate.<h4>Interpretation</h4>Perioperative camrelizumab plus rivoceranib significantly improved EFS compared with surgery alone in patients with resectable hepatocellular carcinoma at intermediate or high risk of recurrence.<h4>Funding</h4>Shanghai Hospital Development Center and Jiangsu Hengrui Pharmaceuticals.","is_dataset_classified":null,"base_score":3.8712010109078907,"endowment":3.8712010109078907,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41125112","pmcid":null,"openalex_id":"https://openalex.org/W4415331968","authors":[],"funders":[{"funder_name":"Shanghai Hospital Development Center","grant_id":"SHDC2020CR1022B","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82488101","title":null},{"funder_name":"Jiangsu Hengrui Medicine","grant_id":"","title":null},{"funder_name":"Science and Technology Commission of Shanghai Municipality","grant_id":"","title":null}],"total_grants":4,"fwci":30.0923,"citation_percentile":0.99810832,"influential_citations":0,"citation_trend":[{"year":2025,"count":3},{"year":2026,"count":44}],"oa_status":"closed","license":"https://doi.org/10.15223/policy-004","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0140673625017209?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0140673625017209?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/s0140-6736(25)01720-9","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41125112","host_type":"repository"}],"fields_of_study":["Hepatocellular Carcinoma Treatment and Prognosis","Cancer, Stress, Anesthesia, and Immune Response","Cancer Immunotherapy and Biomarkers"],"mesh_terms":["Adult","Aged","Antineoplastic Agents","Antineoplastic Combined Chemotherapy Protocols","China","Female","Hepatectomy","Carcinoma, Hepatocellular","Humans","Liver Neoplasms","Male","Middle Aged","Neoplasm Recurrence, Local","Neoplasm Staging","Pyridines","Chemotherapy, Adjuvant","Neoadjuvant Therapy","Protein Kinase Inhibitors","Antibodies, Monoclonal, Humanized"],"keywords":["Perioperative","Hepatocellular carcinoma","Overall survival","Randomized controlled trial","Clinical trial","Resection","Carcinoma"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T10:38:22.255972Z","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":[]}