An International Phase 4 Study of Lenvatinib and Sorafenib in Real-World Patients with Unresectable Hepatocellular Carcinoma: Final Analysis

Introduction: The phase 3 REFLECT trial demonstrated the efficacy and safety of lenvatinib versus sorafenib in the first-line treatment of patients with unresectable hepatocellular carcinoma (uHCC). We report results from STELLAR, a non-interventional post-marketing study. The primary objectives were to characterize hepatotoxicity and overall safety of lenvatinib in patients from Western regions with uHCC. Methods: STELLAR was a prospective, open-label, observational, phase 4 study of patients treated with lenvatinib (n = 193). A cohort of sorafenib-treated patients (n = 123) was included as an internal reference group. The treating physician made the decision to treat patients with lenvatinib or sorafenib before enrollment. Study drugs were administered according to the Summary of Product Characteristics guidelines. Safety and efficacy evaluations were performed according to standard clinical practice at each site. The primary endpoint was safety. Secondary endpoints included treatment exposure and overall survival. Results: The median duration of treatment with lenvatinib or sorafenib was 6.5 months (range, 0.2–33.1 months) and 4.4 months (range, 0.5–30.7 months), respectively. Hepatotoxicity treatment-emergent adverse events (TEAEs) were observed in 26.9% of lenvatinib-treated patients and 33.3% of sorafenib-treated patients. The most frequently reported hepatotoxicity TEAEs were hepatic encephalopathy (7.8%; lenvatinib cohort) and ascites (11.4%; sorafenib cohort), respectively. Overall, 85.0% of lenvatinib-treated patients and 84.6% of sorafenib-treated patients experienced ≥1 TEAE. Median OS (95% CI) was 16.9 months (14.1–not estimable) in lenvatinib-treated patients. Conclusion: Our findings support the established safety and efficacy of lenvatinib in first-line patients with uHCC.