Sintilimab and lenvatinib plus hepatic arterial infusion chemotherapy and embolization as conversion therapy for uHCC: A phase 2 trial

Clinical Snapshot

Key Findings

• P Value: PFS comparison p=0.020, OS comparison p=0.029

• Effect Size: Objective response rate: 80.7% (mRECIST), 43.8% (RECIST 1.1)

• Primary Outcome: Conversion-to-resection rate: 77.2% (44/57 patients)

• Nnt Or Sensitivity: Number needed to treat approximately 1.3 patients for one additional conversion to resection compared to historical controls

• Confidence Interval: Conversion rate 95% CI: 0.64-0.87

Clinical Application

Requires specialised hepatobiliary centre with interventional radiology capabilities, immunotherapy and targeted therapy access, and multidisciplinary team coordination Sintilimab not currently TGA-approved; lenvatinib available on PBS for HCC. TACE-HAIC requires specialised centres. Consider in context of existing HCC treatment pathways and referral to hepatobiliary centres Patients with unresectable hepatocellular carcinoma who are candidates for intensive multimodal therapy and have adequate performance status

Abstract

BACKGROUND: Transarterial chemoembolization (TACE) or systemic treatments are recommended for unresectable hepatocellular carcinoma (uHCC) but have low conversion-to-resection rates. This single-arm phase II trial (PLATIC) aims to investigate the conversion efficacy of PD-1 inhibitor sintilimab, lenvatinib plus TACE and hepatic arterial infusion chemotherapy (TACE-HAIC) in uHCC. METHODS: 57 uHCC patients received 200 mg of sintilimab and lenvatinib (8/12 mg for body weight <60 kg or ≥60 kg) and TACE-HAIC every 3-4 weeks. The primary endpoint was conversion-to-resection rate. A historical-based cohort treated with TACE-HAIC was included as control. FINDINGS: After a median of three treatment cycles, 44 (77.2%; 95% confidence interval [CI], 0.64-0.87]) patients underwent conversion resection. The objective response rates were 80.7% (95% CI, 0.68-0.90) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) and 43.8% (95% CI, 0.31-0.58) according to RECIST 1.1. Grade ≥ 3 treatment-related adverse events (TRAEs) occurred in 37 (64.9%) patients; no treatment-related deaths were reported. Among the 44 patients receiving resection, the median progression-free survival (PFS) was 17.3 months, and the median overall survival (OS) was unavailable. After inverse probability of treatment weighting analysis, the PLATIC cohort exhibited longer PFS (hazard ratio [HR] = 0.55, 95% CI, 0.33-0.94; p = 0.020) and OS (HR, 0.50, 95% CI, 0.28-0.92; p = 0.029) than the historical cohort. CONCLUSIONS: Sintilimab, lenvatinib, and TACE-HAIC demonstrated favorable conversion-to-resection rates and acceptable TRAEs in uHCC. FUNDING: Supported by grants from the National Natural Science Foundation of China (no. 82172815 and 82272887) and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center (no. PT22040201).

References

1. 1.Qiu, J., Huang, Z., He, W., Wang, C., Xie, C., Shen, J., Cai, M., Yuan, Y., Zou, R., Li, B., & Yuan, Y. (2026). Sintilimab and lenvatinib plus hepatic arterial infusion chemotherapy and embolization as conversion therapy for uHCC: A phase 2 trial. Med (New York, N.Y.). https://doi.org/10.1016/j.medj.2026.101132