Full-coverage therapy for converting unresectable advanced hepatocellular carcinoma.

Abstract

e16238 Background: Unresectable advanced HCC remains a major clinical challenge, with limited treatment options and suboptimal outcomes. Achieving tumor conversion through effective systemic therapy followed by curative intervention is a key approach to improving survival. Current conversion strategies that combine antiangiogenic agents with ICIs plus TACE or HAIC have demonstrated ORRs of 60–80% and conversion rates of 30–60%. To potentially enhance this approach, we developed a therapy termed 'Full Coverage,' which incorporates oral capecitabine into the FOLFOX HAIC regimen with bevacizumab and camrelizumab. This addition aims to maintain continuous 5-FU exposure throughout the treatment cycle, potentially improving treatment efficacy. Methods: Patients with advanced HCC (Child-Pugh class A/B) were treated in 4-week cycles. On Days 1–3, they received HAIC (oxaliplatin 100 mg/m^2, leucovorin 100 mg/m^2, 5-FU 0.75 g bolus plus 3.25 g continuous infusion over 46 hours), along with IV bevacizumab (500 mg) and camrelizumab (200 mg) on Day 4. From Days 8 to 21, patients took oral capecitabine at 1250 mg/m^2 twice daily. Therapy continued until conversion or PD or unacceptable toxicity. Results: Fifteen patients (median age 55 [range 43–73]; 13 male, 2 female) were enrolled between Jun 2022 and Oct 2024. As of the data cutoff (Dec 2024), 1 achieved CR, 12 PR, 1 SD, and 1 PD, yielding an ORR of 86.7% and a DCR of 93.3%. Ten patients (66.7%) converted to curative treatment: 4 underwent surgery (3 hepatectomies, 1 transplantation), 2 received curative SBRT, 1 had RFA, 2 declined suggested curative intervention and switched to lenvatinib plus camrelizumab for maintenance therapy, and 1 achieved CR received no additional treatment. Among converted patients, 3 experienced recurrence: 2 post-surgical patients remain alive, while 1 patient who denied to receive curative treatment died after 22 months. Of the remaining 5 non-converted patients, 2 maintained PR at data cutoff. For all patients, median PFS was 8.0 mo (95% CI 5.1–13.7), and median OS was 9.9 mo (95% CI 6.7–22.2). In converted patients, median PFS and OS were 10.9 mo (95% CI 8.2-15.5) and 13.6 mo (95% CI 10.1–20.7), respectively. Common AEs were HAIC related (nausea, pain, transient transaminase elevations), ICI related (reactive cutaneous capillary endothelial proliferation), and capecitabine related (hand-foot syndrome, leukopenia, thrombocytopenia), predominantly G1-2 and manageable. No treatment-related SAEs were observed. Conclusions: Full-Coverage Therapy—extending 5-FU with oral capecitabine—produced an ORR of 86.7% and a 66.7% conversion rate in unresectable advanced HCC, exceeding reported outcomes of current systemic regimens. This pilot study indicates that prolonged 5-FU exposure is feasible, effective, and well tolerated. Larger trials are needed to confirm these findings and clarify long-term benefits.