Hepatic arterial infusion chemotherapy plus either toripalimab or sorafenib as first-line therapy for non–high-risk, locally advanced hepatocellular carcinoma: A non-comparative, randomized phase 2 trial.

4115 Background: A combination of locoregional therapy such as hepatic arterial infusion chemotherapy (HAIC) with anti-angiogenic agents and immune checkpoint inhibitors (ICIs), has demonstrated significant antitumor activity in advanced hepatocellular carcinoma (HCC), while inevitably increasing the incidence of adverse events (AEs). Given the clinical rationale for exploring treatment de-escalation in non-high-risk, locally advanced HCC, this study was designed to provide prospective evidence for the combination of HAIC and toripalimab, which had suggested encouraging antitumor activity and safety previously. Methods: This single-center, non-comparative, randomized phase II study (NCT04135690) recruited locally advanced HCC participants without high-risk features (Vp4, and/or bile duct invasion and/or tumor occupancy of 50% of the liver). Participants were randomly assigned at a 1:1 ratio to receive FOLFOX-HAIC plus either toripalimab (240mg intravenously, TorHAIC) or sorafenib (400mg orally twice daily, SoraHAIC) per 3 weeks. The primary endpoint was the progression-free survival (PFS) rate at 6 months. Results: From February 4, 2020, to December 17, 2021, 72 participants were randomly assigned to receive TorHAIC (n = 36) or SoraHAIC (n = 36). The mean tumor diameter was 9.9 cm. Vp1-2 and Vp3 portal vein tumor thrombosis were present in 46 (63.9%) and 26 (36.1%) participants, respectively. The 6-month PFS rate was 63.9% in the TorHAIC group and 61.1% in the SoraHAIC group. After a median follow-up of 45.2 months, the median overall survival was 20.9 months in the TorHAIC group and 16.4 months in the SoraHAIC group, while the median PFS was 9.1 and 7.2 months, respectively. The objective response rate per RECIST v1.1 was 52.8% (n = 19) in the TorHAIC group, whereas 47.2% (n = 17) in the SorHAIC group. The median duration of response was 9.8 months in the TorHAIC group and 6.8 months in the SorHAIC group. There were 12 participants (33.3%) who developed grade 3-4 AEs in the TorHAIC group and 16 participants (44.4%) in the SoraHAIC group. Serious AEs were reported in two participants in the TorHAIC group (laryngeal edema due to oxaliplatin allergy and thrombocytopenia) and five participants in the SoraHAIC group (impaired myeloid function n = 3, renal impairment, and upper gastrointestinal bleeding). Conclusions: Our study suggested that the TorHAIC regimen had a favorable safety and efficacy profile in patients with non-high-risk, locally advanced HCC. However, these findings warrant validation in a phase III trial. Clinical trial information: NCT04135690 .