TACE plus lenvatinib and envafolimab for conversion therapy in unresectable HCC: a prospective pilot study

Background: Most patients with hepatocellular carcinoma (HCC) are diagnosed at intermediate or advanced stages, when curative resection is not feasible. Conversion therapy aiming to downstage tumors and enable surgical resection has emerged as a potential strategy. We performed an exploratory, single-arm pilot study to assess the efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib and the envafolimab in this setting. Methods: This single-center, open-label, single-arm pilot trial enrolled patients with Barcelona Clinic Liver Cancer stage B or C unresectable HCC between April and September 2024. Patients received conventional TACE combined with oral lenvatinib and subcutaneous envafolimab until surgical conversion, disease progression, unacceptable toxicity, or death. The primary endpoint was the conversion rate to curative-intent resection. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), pathological response, progression-free survival (PFS), overall survival (OS), and safety. Results: Fifteen patients were enrolled. According to mRECIST criteria, the ORR was 53.3% and the DCR was 86.7%. Nine patients (60.0%) achieved sufficient tumor downstaging to undergo curative-intent surgery, and all achieved R0 resection. Pathological complete or major response was observed in five resected patients (55.6%). After a median follow-up of 16 months, the estimated median PFS was 12.0 months. One patient died during follow-up, yielding a 1-year OS of 100% and an 18-month OS of 93.3%. Treatment-emergent adverse events were consistent with the known profiles of TACE, lenvatinib, and envafolimab; however, gastrointestinal bleeding was observed and represents an important safety concern that warrants careful risk stratification and proactive management. Conclusion: In this small pilot study, TACE combined with lenvatinib and envafolimab was associated with encouraging antitumor activity and a relatively high conversion-to-resection rate, with an acceptable safety profile. However, the limited sample size and single-arm design preclude definitive causal conclusions, and gastrointestinal bleeding emerged as an important risk. These preliminary findings suggest the need for validation in larger, controlled trials. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=222901, identifier ChiCTR2400081945.