A Novel Quadruple Conversion Therapy: Converting Initially Unresectable Hepatocellular Carcinoma to Resectable with pTAE-HAIC, Tyrosine Kinase Inhibitors, and Anti-PD-1 Antibodies.

Abstract

Purpose: The aim of this study was to evaluate the potential of partial transcatheter arterial embolization (pTAE)-hepatic artery infusion chemotherapy (HAIC) in combination with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies for downstaging and subsequent resection in patients with initially unresectable hepatocellular carcinoma (HCC).

Methods: Patients with unresectable HCC who underwent initial treatment with a combination of pTAE, HAIC, TKIs, and an anti-PD-1 antibody were studied. The tumour response and potential for resection were assessed through imaging every month (±1 week) using RECIST v1.1.

Results: Among 17 patients (27.4%) who achieved R0 resection, the median time from quadruple therapy initiation to surgery was 89 days (range: 69-255). The cohort comprised 13 males and 4 females, with a median age of 51 years (range: 18-70). Twelve patients had BCLC stage C disease, including 11 with major vascular invasion (Vp2, Vp3, Vv2, Vv3, Vv1) and 3 with concurrent portal and hepatic venous invasion (Vp2/Vv2, Vp3/Vv2, Vp3/Vv3). Five patients had BCLC stage B HCC. The median diameter of the largest liver nodule was 11.5 cm (range: 3.9-18.8), with 10 patients presenting multiple lesions. Preoperatively, 17 patients underwent 43 cycles of pTAE-HAIC (median: 2, range: 1-5). Based on RECIST v1.1, 13 patients achieved partial response (PR), and 4 had stable disease (SD). With a median follow-up of 17.8 months (range: 12.2-38.3), the 12-month overall survival post-hepatectomy was 100%, and the median progression-free survival (PFS) was 14.5 months (range: 1.5-31.8). Tumor recurrence within 12 months occurred in 5 patients, with 4 achieving disease control after additional treatment.

Conclusion: Quadruple therapy, consisting of pTAE-HAIC combined with TKIs and anti-PD-1 antibodies, represents a feasible conversion strategy for patients with unresectable HCC to achieve successful resection and potential long-term survival.