Safety and Effectiveness of Hepatic Arterial Infusion Chemotherapy Combined With Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors for Advanced Hepatocellular Carcinoma in BCLC Stage C

Abstract

Background: To assess the safety and efficacy of a combination therapy consisting of hepatic arterial infusion chemotherapy (HAIC) of Oxaliplatin, Fluorouracil, and Leucovorin (FOLFOX), tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) (TRIPLET) for patients with advanced hepatocellular carcinoma (HCC) in BCLC Stage C. \n \nMethods: This retrospective study was approved by the ethical review committee, and informed consent was obtained from all patients. 22 patients with initial presentation or recurrent HCC in BCLC Stage C received HAIC plus TKI plus ICI (TRIPLET) treatment from April 1, 2019, to April 30, 2020. The primary endpoint was objective response. The second endpoint were survival outcomes and safety. \n \nFindings: The best overall response was 59.1% per RECIST 1.1 and 81.8% per mRECIST. The median duration of response was 9.83 months per mRECIST. The DCR was 100% per both RECIST and mRECIST. Complete response (CR) was achieved in 7 patients (31.8%) per mRECIST. The median overall progression free survival (PFS) time in the cohort was 11.17 months (95% CI 5.87 - 16.46) per mRECIST. The estimated 6- and 12-month overall PFS rates were 82.7% and 42.7%, respectively. The estimated 6- and 12-month OS rates were 93.8% and 93.8%, respectively. Grade 3 adverse events occurred in 15 patients (68.2%) and were all reversible. Grade 4 adverse events occurred in 4 patients (18.2%) all with transient bone marrow suppression. \n \nConclusion: HAIC plus TKI plus ICI (TRIPLET) has promising survival benefits in the management of advanced hepatocellular carcinoma in BCLC Stage C with tolerable safety. \n \nFunding Statement: This work was supported by the Guangzhou Science and Technology Program, civic technology research plan (No. 201903010037). \n \nDeclaration of Interests: The authors declare that they have no conflict of interest. \n \nEthics Approval Statement: The informed consent was obtained from all patients. All patients were followed up under the hospital ethics committee approval of SYSUCC (B2020-243-01). The principles of the Declaration of Helsinki were followed.