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

Jing Xiao,1,2 Qingdong Li,2 Wentao Zheng,2 Kaiyou Liao,2 Qianwen Yu,2 Rongzhong Huang,1 Rong Zhou2 1Precision Medicine Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, People’s Republic of ChinaCorrespondence: Rongzhong Huang, Email [email protected] Rong Zhou, Email [email protected]: 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.Keywords: hepatocellular carcinoma, conversion therapy, transcatheter arterial embolization, hepatic artery infusion chemotherapy, tyrosine kinase inhibitor, anti-PD-1 antibody