Hepatic artery infusion chemotherapy combined with donafenib and camrelizumab in patients with unresectable hepatocellular carcinoma presenting portal vein tumor thrombus: A prospective, single-arm study.
Authors: He Qiang , Wu Chenrui , Pan Long , Li Jiachu , Zhou Yin , Cao Hongxiang , Sun Ruirui , Huang Junjie , Wang Yongchen , Huang Ping 
Published: June 2023

e16134 Background: Rational and effective treatment strategies for patients with unresectable hepatocellular carcinoma (uHCC) presenting portal vein tumor thrombus (PVTT) are lacking, and hepatic artery infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors and immune checkpoint inhibitors could be an effective therapy. Herein, we evaluated the efficacy and safety of HAIC combined with donafenib and camrelizumab in patients with uHCC presenting PVTT. Methods: This prospective, single-arm, single-center study enrolled patients with uHCC presenting PVTT (distant metastases were allowed), BCLC stage C, Child-Pugh scores ≤ 7, ECOG PS ≤1, and no previous local or systemic treatment. Patients received mFOLFOX6-HAIC (every 3 weeks, no more than 6 cycles), followed by peroral donafenib (200 mg BID every day) and intravenous camrelizumab (200 mg every 3 weeks). The primary endpoint was the objective response rate (ORR; per RECIST1.1 and mRECIST). Secondary endpoints included surgical conversion rate, disease control rate, progression-free survival (PFS), overall survival (OS), duration of response, and safety. Results: Between November 2021 and September 2022, we enrolled 15 eligible patients with a median age of 53 years (range, 36-76), including 12 (80%) males. Considering enrolled patients, 14 (93.3%) were HBV+, 13(86.7%) presented with PVTT invasion into the main portal vein, Child-Pugh scores 5/6/7: 9/5/1, ECOG PS 0/1: 10/5, median tumor size was 8.4 cm (range, 5.2-13.6), and 5 (33.3%) had extrahepatic metastases. The median number of HAIC procedures was 5 (range, 1-6). The median follow-up time was 338.0 days (95% CI, 298.7-377.4). Considering the 15 evaluable patients (completed at least one cycle of treatment), the ORR was 66.7% (10/15) according to RECIST 1.1, with 0 complete response (CR) and 10 partial responses (PR). According to mRECIST, the ORR was 73.3% (11/15), with 2 CR and 9 PR. Three patients (20%) became eligible for surgical resection, with one undergoing surgical resection (two refused surgery for financial reasons). Median PFS and OS were insufficient. All 15 (100%) patients experienced treatment-related adverse events (TRAEs). Common TRAEs included hand-and-foot skin reaction (HFSR; 93.3%), abdominal pain (73.3%), hypoalbuminemia (60.0%), platelet count decreased (60.0%), nausea (60%), aspartate aminotransferase increased (53.3%), and vomiting (53.3%). Grade 3/4 TRAEs included platelet count decreased (13.3%), HFSR (13.3%), hepatic function abnormal (6.7%), and ascites (6.7%). No grade 5 TRAEs were observed. TRAEs led to drug reduction in 8 patients (53.3%). Conclusions: HAIC combined with donafenib and camrelizumab afforded promising efficacy and safety in patients with uHCC presenting PVTT. Longer follow-up is required for further evaluation. Clinical trial information: ChiCTR2100051714 .