Clinical outcomes with first-line tislelizumab plus lenvatinib in unresectable hepatocellular carcinoma: a retrospective analysis

Purpose: This retrospective analysis aimed to assess the therapeutic efficacy and adverse event profile of tislelizumab combined with lenvatinib in patients with unresectable hepatocellular carcinoma (uHCC), predominantly of hepatitis B virus (HBV) etiology. While this combination has shown promise in clinical trials, real-world data in HBV-endemic populations remain sparse. Methods: A total of 163 uHCC patients who initiated first-line systemic therapy with tislelizumab and lenvatinib between January 2021 and February 2025 were retrospectively analyzed. Treatment response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Key clinical endpoints included objective response rate (ORR), overall survival (OS), progression-free survival (PFS), disease control rate (DCR), treatment-emergent adverse events (TRAEs), and other relevant outcomes. Prognostic factors were explored through subgroup analyses and multivariate Cox proportional hazards modeling. Results: Of the 163 patients (84.7% HBV-related), the ORR was 25.8%, DCR was 67.5%, and median PFS was 13.87 months. Additionally, 16.6% of patients achieved conversion therapy and subsequent surgical resection. Subgroup and multivariate analyses indicated that a larger tumor burden, particularly tumors ≥5 cm, was associated with shorter PFS but did not significantly affect OS. TRAEs were observed in 86% of patients, with grade ≥3 events occurring in 5%. Conclusions: This analysis supports that tislelizumab plus lenvatinib provides substantial clinical benefit in HBV-related uHCC, including potential for conversion to surgical resection. Tumor burden emerged as a key predictor of progression. The regimen demonstrated a favorable safety profile, reinforcing its potential as a frontline treatment in HBV-endemic areas.