Real-World Comparison of Lenvatinib and Sorafenib as First-Line Treatments for Hepatocellular Carcinoma: A Multicenter Study.

Introduction: Lenvatinib and sorafenib remain viable first-line (1L) options for patients ineligible for newer therapies. This study uses real-world data (RWD) to compare the effectiveness and safety of lenvatinib and sorafenib, addressing gaps between clinical trials and real-world practice. Materials and Methods: This retrospective, multi-center study utilized the Liver Cancer IN Korea (LINK) database, including HCC patients diagnosed between January 2015 and June 2022 who received 1L lenvatinib or sorafenib. Effectiveness and safety were assessed with real-world overall survival (rwOS), time to treatment discontinuation (rwTTD), time to next treatment (rwTTNT), and incidence of adverse events of special interest (AESI). Propensity score matching was employed to adjust for potential bias. Results: Post-matching, lenvatinib demonstrated a longer median rwOS of 9.56 months (95% CI: 8.25-10.78) compared to 7.13 months (95% CI: 6.44-7.82) of sorafenib, and longer medians for rwTTD (3.65 months, 95% CI: 3.09-4.07 vs 2.04 months, 95% CI: 1.87-2.30) and rwTTNT (6.51 months, 95% CI: 5.62-7.62 vs 3.71 months, 95% CI: 3.45-4.34). Regarding AESI, lenvatinib was significantly associated with lower rates of hand-foot syndrome (incidence rate ratio, IRR 0.55, 95% CI: 0.33-0.88, p = 0.013) and most hepatotoxicity-related events, but a higher rate of proteinuria (IRR 2.40, 95% CI: 1.49-3.98, p < 0.001). Conclusion: Leveraging RWD, our study demonstrated that 1L lenvatinib may offer a survival advantage over 1L sorafenib in HCC patients, with both treatments exhibiting safety profiles consistent with clinical trials. RWD complements clinical trials by validating long-term outcomes and addressing patient populations excluded from pivotal studies, guiding therapeutic decisions in clinical practice.