First-Line Lenvatinib plus Pembrolizumab for Hepatocellular Carcinoma: Post hoc Analysis of Japanese Patients from the Phase 3 LEAP-002 Trial.

Introduction: The phase 3 LEAP-002 study (NCT03713593) of advanced hepatocellular carcinoma (HCC) suggested improved antitumor activity of lenvatinib plus pembrolizumab versus lenvatinib alone with manageable safety, although overall survival (OS) and progression-free survival (PFS) did not reach prespecified statistical significance. This post hoc analysis assessed efficacy and safety in Japanese patients.

Methods: Patients with advanced HCC without prior systemic treatment were randomly assigned 1:1 to receive 8 mg (body weight <60 kg) or 12 mg (body weight ≥60 kg) oral lenvatinib once daily plus 200 mg intravenous pembrolizumab or placebo every 3 weeks for up to 35 cycles. Dual primary end points were OS and PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary end points were objective response rate, disease control rate, duration of response, and time to progression per RECIST v1.1 by BICR and safety.

Results: Overall, 80 patients were enrolled in Japan (lenvatinib plus pembrolizumab, = 39; lenvatinib plus placebo, = 41). Median time from randomization to database cutoff (June 21, 2022) was 34.1 months (range: 26.9-39.6). Median OS was 31.4 months (95% CI: 21.2- not reached) for lenvatinib plus pembrolizumab and 21.4 months (95% CI: 14.4-25.4) for lenvatinib plus placebo (hazard ratio [HR] = 0.55 [95% CI: 0.31-0.96]). Median PFS for lenvatinib plus pembrolizumab was 10.4 months (95% CI: 6.2-18.5) and 6.5 months (95% CI: 6.0-8.3) for lenvatinib plus placebo (HR = 0.54 [95% CI: 0.32-0.90]). Grade 3 or 4 treatment-related adverse events occurred in 26 patients (67%) in the lenvatinib plus pembrolizumab group and 24 patients (59%) in the lenvatinib plus placebo group.

Conclusion: In Japanese patients enrolled in LEAP-002, findings were consistent with the global population where OS and PFS trended toward improvement; a similar safety profile was observed.