Hepatic arterial infusion chemotherapy plus sintilimab as conversion therapy for locally advanced hepatocellular...

Patients with locally advanced hepatocellular carcinoma (aHCC) who have macroscopic vascular invasion typically have a poor prognosis. As the understanding of interventional therapy evolves, the conversion therapy strategy based on interventional approaches can significantly enhance objective response and raise the chance of resection for these patients. While the long-term outcomes of the conversion-to-surgery strategy remain unclear. In this article, we report the results of a phase II clinical trial that focused on the survival benefits and safety of conversion-to-surgery therapy, utilizing hepatic arterial infusion chemotherapy of infusion fluorouracil, leucovorin, and oxaliplatin (FOLFOX-HAIC) combined with sintilimab for locally aHCC.

This open-label, single-center, two-cohort phase II study recruited a total of 40 patients who had initially unresectable HCC within SYSUCC criteria between March 2019 and July 2020. Patients received FOLFOX-HAIC, combined with intravenous sintilimab (cohort A, N = 30) or not (cohort B, N = 10) every 3 weeks for up to eight courses. Patients who achieved tumor shrinkage and were eligible for surgery received radical resection or ablation, then received sintilimab monotherapy up to 16 doses in total (cohort A) or supportive care (cohort B). The primary endpoint was progression-free survival (PFS) assessed with the Response Evaluation Criteria in Solid Tumors version 1.1.

Of the total 40 subjects, the median age was 50 years (range, 29-70 years). With a median follow-up of 52.9 months (range, 6.6-68.6 months). The median PFS was 19.8 months [95% confidence interval (95% CI), 8.2 months-not reached (NR)] in cohort A, and 17.6 months (95% CI, 4.13 months-NR) in cohort B. The conversion rate was beyond 70% in both cohorts. Of the 26 patients (19 in cohort A and 7 in cohort B) who received liver resection, 4 of cohort A (21%) and 1 of cohort B (14%) achieved pathological complete response. The 5-year overall survival rate of the whole study population was 56.3% (95% CI, 43-74%).

Hepatic arterial infusion chemotherapy plus sintilimab exhibited impressive outcomes and safety as a conversion therapy for locally aHCC.