Donafenib and sintilimab combined with hepatic arterial infusion chemotherapy for unresectable hepatocellular carcinoma: a prospective, single-arm phase II trial (DoHAICs study)Research in context
Summary: Background: Donafenib demonstrates superior survival benefits and safety compared to sorafenib. Hepatic arterial infusion chemotherapy (HAIC) proves effective for large unresectable hepatocellular carcinoma (uHCC) over transarterial chemoembolization. This study aims to investigate the saf...
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Elsevier
2025-05-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S258953702500149X |
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| author | Wei Gao Zhao-Long Pan Xiao-Hui Zhao Lu Yang Jun-Bo Cao Dong-Yang Li Hai-Jing Zheng Chen Liu Guang-Tao Li Xu Bao Xiao-Meng Liu Wei-Hao Zhang Xiao-Lin Zhu Bo-Han Xiao Tian-Qiang Song Qiang Li Wei Lu Wen-Ge Xing Wei Zhang |
| author_facet | Wei Gao Zhao-Long Pan Xiao-Hui Zhao Lu Yang Jun-Bo Cao Dong-Yang Li Hai-Jing Zheng Chen Liu Guang-Tao Li Xu Bao Xiao-Meng Liu Wei-Hao Zhang Xiao-Lin Zhu Bo-Han Xiao Tian-Qiang Song Qiang Li Wei Lu Wen-Ge Xing Wei Zhang |
| author_sort | Wei Gao |
| collection | DOAJ |
| description | Summary: Background: Donafenib demonstrates superior survival benefits and safety compared to sorafenib. Hepatic arterial infusion chemotherapy (HAIC) proves effective for large unresectable hepatocellular carcinoma (uHCC) over transarterial chemoembolization. This study aims to investigate the safety and efficacy of combining HAIC with donafenib and sintilimab in patients with uHCC. Methods: This prospective single-arm study enrolled patients with histologically confirmed uHCC and no prior systemic treatment from December 2021 to May 2023 in Tianjin Medical University Cancer Institute and Hospital, China. Participants received donafenib, sintilimab and HAIC until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR). The secondary endpoints included overall survival (OS), event-free survival (EFS), disease control rate (DCR) and safety. The study was registered at ClinicalTrials.gov, NCT05166772. Findings: A total of 36 patients were enrolled, and the median follow-up was 16 months. ORR were 58.3% and 80.6% per RECIST 1.1 and mRECIST respectively, and DCR were all 94.4%. 24-month OS rate was 59.6%. Median EFS was 15.3 months. The conversion success rate was 50.0%, 18 patients underwent hepatectomy, seven (38.9%) achieved pathological complete response, and nine (50.0%) achieved major pathological responses. Median OS was not achieved (NA) in the surgical group vs. 14.3 months (95% CI 12.1–NA) in the non-surgical group (p = 0.035). Adverse reactions were manageable. Interpretation: Combining HAIC with donafenib and sintilimab demonstrates promising clinical outcomes while maintaining acceptable toxicity, making it a potential strategy for conversion therapy. Funding: Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-009A) and Precision Treatment Project of Surgical Oncology of Tianjin Medical University Cancer Institute and Hospital (No. ZLWKJZZL14). |
| format | Article |
| id | doaj-art-bb6f15e4319645018ecfead5161cbc5b |
| institution | Kabale University |
| issn | 2589-5370 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj-art-bb6f15e4319645018ecfead5161cbc5b2025-08-20T03:48:46ZengElsevierEClinicalMedicine2589-53702025-05-018310321710.1016/j.eclinm.2025.103217Donafenib and sintilimab combined with hepatic arterial infusion chemotherapy for unresectable hepatocellular carcinoma: a prospective, single-arm phase II trial (DoHAICs study)Research in contextWei Gao0Zhao-Long Pan1Xiao-Hui Zhao2Lu Yang3Jun-Bo Cao4Dong-Yang Li5Hai-Jing Zheng6Chen Liu7Guang-Tao Li8Xu Bao9Xiao-Meng Liu10Wei-Hao Zhang11Xiao-Lin Zhu12Bo-Han Xiao13Tian-Qiang Song14Qiang Li15Wei Lu16Wen-Ge Xing17Wei Zhang18Department of Interventional Therapy, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Hepatobiliary Surgery, Liver Cancer Prevention and Treatment Research Center, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China; National Clinical Research Center for Cancer, Tianjin, China; Tianjin’s Clinical Research Center for Cancer, Tianjin, China; Tianjin Key Laboratory of Digestive Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, ChinaDepartment of Interventional Therapy, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Hepatobiliary Surgery, Liver Cancer Prevention and Treatment Research Center, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China; National Clinical Research Center for Cancer, Tianjin, China; Tianjin’s Clinical Research Center for Cancer, Tianjin, China; Tianjin Key Laboratory of Digestive Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, ChinaDepartment of Hepatobiliary Surgery, Liver Cancer Prevention and Treatment Research Center, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China; National Clinical Research Center for Cancer, Tianjin, China; Tianjin’s Clinical Research Center for Cancer, Tianjin, China; Tianjin Key Laboratory of Digestive Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, ChinaDepartment of Hepatobiliary Surgery, Liver Cancer Prevention and Treatment Research Center, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China; National Clinical Research Center for Cancer, Tianjin, China; Tianjin’s Clinical Research Center for Cancer, Tianjin, China; Tianjin Key Laboratory of Digestive Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, ChinaDepartment of Hepatobiliary Surgery, Liver Cancer Prevention and Treatment Research Center, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China; National Clinical Research Center for Cancer, Tianjin, China; Tianjin’s Clinical Research Center for Cancer, Tianjin, China; Tianjin Key Laboratory of Digestive Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, ChinaDepartment of Hepatobiliary Surgery, Liver Cancer Prevention and Treatment Research Center, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China; National Clinical Research Center for Cancer, Tianjin, China; Tianjin’s Clinical Research Center for Cancer, Tianjin, China; Tianjin Key Laboratory of Digestive Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, ChinaDepartment of Hepatobiliary Surgery, Liver Cancer Prevention and Treatment Research Center, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China; National Clinical Research Center for Cancer, Tianjin, China; Tianjin’s Clinical Research Center for Cancer, Tianjin, China; Tianjin Key Laboratory of Digestive Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, ChinaDepartment of Hepatobiliary Surgery, Liver Cancer Prevention and Treatment Research Center, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China; National Clinical Research Center for Cancer, Tianjin, China; Tianjin’s Clinical Research Center for Cancer, Tianjin, China; Tianjin Key Laboratory of Digestive Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, ChinaDepartment of Hepatobiliary Surgery, Liver Cancer Prevention and Treatment Research Center, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China; National Clinical Research Center for Cancer, Tianjin, China; Tianjin’s Clinical Research Center for Cancer, Tianjin, China; Tianjin Key Laboratory of Digestive Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, ChinaDepartment of Interventional Therapy, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Hepatobiliary Surgery, Liver Cancer Prevention and Treatment Research Center, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China; National Clinical Research Center for Cancer, Tianjin, China; Tianjin’s Clinical Research Center for Cancer, Tianjin, China; Tianjin Key Laboratory of Digestive Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, ChinaDepartment of Radiology, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University, Tianjin, ChinaDepartment of Hepatobiliary Surgery, Liver Cancer Prevention and Treatment Research Center, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China; National Clinical Research Center for Cancer, Tianjin, China; Tianjin’s Clinical Research Center for Cancer, Tianjin, China; Tianjin Key Laboratory of Digestive Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, ChinaDepartment of Hepatobiliary Surgery, Liver Cancer Prevention and Treatment Research Center, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China; National Clinical Research Center for Cancer, Tianjin, China; Tianjin’s Clinical Research Center for Cancer, Tianjin, China; Tianjin Key Laboratory of Digestive Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, ChinaDepartment of Hepatobiliary Oncology, Liver Cancer Prevention and Treatment Research Center, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China; National Clinical Research Center for Cancer, Tianjin, China; Tianjin’s Clinical Research Center for Cancer, Tianjin, China; Tianjin Key Laboratory of Digestive Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, ChinaDepartment of Interventional Therapy, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin, China; Corresponding author. Department of Interventional Therapy, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, West Huan-Hu Rd, Ti Yuan Bei, Hexi District, Tianjin, China.Department of Hepatobiliary Surgery, Liver Cancer Prevention and Treatment Research Center, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China; National Clinical Research Center for Cancer, Tianjin, China; Tianjin’s Clinical Research Center for Cancer, Tianjin, China; Tianjin Key Laboratory of Digestive Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Corresponding author. Department of Hepatobiliary Surgery, Liver Cancer Prevention and Treatment Research Center, Tianjin Medical University Cancer Institute & Hospital; National Clinical Research Center for Cancer; Tianjin’s Clinical Research Center for Cancer; Tianjin Key Laboratory of Digestive Cancer; Key Laboratory of Cancer Prevention and Therapy, West Huan-Hu Rd, Ti Yuan Bei, Hexi District, Tianjin, China.Summary: Background: Donafenib demonstrates superior survival benefits and safety compared to sorafenib. Hepatic arterial infusion chemotherapy (HAIC) proves effective for large unresectable hepatocellular carcinoma (uHCC) over transarterial chemoembolization. This study aims to investigate the safety and efficacy of combining HAIC with donafenib and sintilimab in patients with uHCC. Methods: This prospective single-arm study enrolled patients with histologically confirmed uHCC and no prior systemic treatment from December 2021 to May 2023 in Tianjin Medical University Cancer Institute and Hospital, China. Participants received donafenib, sintilimab and HAIC until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR). The secondary endpoints included overall survival (OS), event-free survival (EFS), disease control rate (DCR) and safety. The study was registered at ClinicalTrials.gov, NCT05166772. Findings: A total of 36 patients were enrolled, and the median follow-up was 16 months. ORR were 58.3% and 80.6% per RECIST 1.1 and mRECIST respectively, and DCR were all 94.4%. 24-month OS rate was 59.6%. Median EFS was 15.3 months. The conversion success rate was 50.0%, 18 patients underwent hepatectomy, seven (38.9%) achieved pathological complete response, and nine (50.0%) achieved major pathological responses. Median OS was not achieved (NA) in the surgical group vs. 14.3 months (95% CI 12.1–NA) in the non-surgical group (p = 0.035). Adverse reactions were manageable. Interpretation: Combining HAIC with donafenib and sintilimab demonstrates promising clinical outcomes while maintaining acceptable toxicity, making it a potential strategy for conversion therapy. Funding: Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-009A) and Precision Treatment Project of Surgical Oncology of Tianjin Medical University Cancer Institute and Hospital (No. ZLWKJZZL14).http://www.sciencedirect.com/science/article/pii/S258953702500149XHepatocellular carcinomaHepatic arterial infusion chemotherapyConversion therapySurgical resectionImmune checkpoint inhibitors |
| spellingShingle | Wei Gao Zhao-Long Pan Xiao-Hui Zhao Lu Yang Jun-Bo Cao Dong-Yang Li Hai-Jing Zheng Chen Liu Guang-Tao Li Xu Bao Xiao-Meng Liu Wei-Hao Zhang Xiao-Lin Zhu Bo-Han Xiao Tian-Qiang Song Qiang Li Wei Lu Wen-Ge Xing Wei Zhang Donafenib and sintilimab combined with hepatic arterial infusion chemotherapy for unresectable hepatocellular carcinoma: a prospective, single-arm phase II trial (DoHAICs study)Research in context EClinicalMedicine Hepatocellular carcinoma Hepatic arterial infusion chemotherapy Conversion therapy Surgical resection Immune checkpoint inhibitors |
| title | Donafenib and sintilimab combined with hepatic arterial infusion chemotherapy for unresectable hepatocellular carcinoma: a prospective, single-arm phase II trial (DoHAICs study)Research in context |
| title_full | Donafenib and sintilimab combined with hepatic arterial infusion chemotherapy for unresectable hepatocellular carcinoma: a prospective, single-arm phase II trial (DoHAICs study)Research in context |
| title_fullStr | Donafenib and sintilimab combined with hepatic arterial infusion chemotherapy for unresectable hepatocellular carcinoma: a prospective, single-arm phase II trial (DoHAICs study)Research in context |
| title_full_unstemmed | Donafenib and sintilimab combined with hepatic arterial infusion chemotherapy for unresectable hepatocellular carcinoma: a prospective, single-arm phase II trial (DoHAICs study)Research in context |
| title_short | Donafenib and sintilimab combined with hepatic arterial infusion chemotherapy for unresectable hepatocellular carcinoma: a prospective, single-arm phase II trial (DoHAICs study)Research in context |
| title_sort | donafenib and sintilimab combined with hepatic arterial infusion chemotherapy for unresectable hepatocellular carcinoma a prospective single arm phase ii trial dohaics study research in context |
| topic | Hepatocellular carcinoma Hepatic arterial infusion chemotherapy Conversion therapy Surgical resection Immune checkpoint inhibitors |
| url | http://www.sciencedirect.com/science/article/pii/S258953702500149X |
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