Lenvatinib (Lenv) plus tislelizumab (Tis) combined with or without transarterial chemoembolization (TACE) in first-line treatment of unresectable hepatocellular carcinoma (uHCC): A prospective, non-randomized, open-label, phase II cohort study.

Abstract

e16169 Background: The synergistic potential of programmed death protein-1 inhibitors and tyrosine kinase inhibitors in treating uHCC has been established. TACE, a cornerstone in uHCC therapy, primes the tumor microenvironment for immunotherapy by releasing neoantigens and inducing ischemia. This study explores the efficacy and safety of Lenv plus Tis, combined with or without TACE, in a first-line setting. Methods: This phase II study enrolled patients (pts) with pathologically and/or radiologically diagnosed uHCC eligible for embolization, with at least one measurable lesion, Child-Pugh class A/B, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Pts received Tis (200mg every 3 weeks) and Lenv (oral dose adjusted by weight: 8mg for <60kg and 12mg for ≥60kg) with or without conventional TACE, as determined by the treating physician. The primary endpoint was the objective response rate (ORR), with secondary endpoints including overall survival (OS), progression-free survival (PFS), and disease control rate (DCR). Results: By the data cutoff on January 27, 2024, 37 pts were enrolled: 12 received Lenv+Tis (cohort 1), and 25 received Lenv+Tis+TACE (cohort 2). Median follow-up time was 10.66 months. The ORR was 33.3% in cohort 1 and 68.0% in cohort 2, with DCRs of 100% and 96%, respectively (mRECIST). Median OS was 10.85 months (95% CI, 4.76-16.95) for cohort 1 and 13.61 months (95%CI, NE-NE) for cohort 2. Median PFS was 10.85 months (95% CI, NE-NE) for cohort 1, and 11.86 months (95% CI, 6.49-16.73) for cohort 2. Grade 3-4 treatment-emergent adverse events (teAE) occurred in 50% of cohort 1 and 68% of cohort 2. No fatal adverse event was reported. The most common grade 3-4 teAE (incidence >10%) were anaemia (17%) in cohort 1, and decreased platelet count (16%), hypertension (16%), rash (16%), fatigue (12%), elevated ALT (12%) in cohort 2. Conclusions: Both Lenv+Tis and Lenv+Tis+TACE showed promising efficacy and manageable safety in the first-line treatment of uHCC. More pts were recruiting to further prove these results. Clinical trial information: NCT05842317 . [Table: see text]