Phase III trial of lenvatinib (LEN) vs sorafenib (SOR) in first-line treatment of patients (pts) with unresectable hepatocellular carcinoma (uHCC).

• DOI: 10.1200/jco.2017.35.15_suppl.4001
• Publication Date: 2018-09-06T15:43:43Z
• Authors: Ann-Lii Cheng; Richard S. Finn; Shukui Qin; Kwang-Hyub Han; Kenji Ikeda; Fabio Piscaglia; Ari David Baron; Joong-Won Park; Guohong Han; Jacek Jassem; Jean-Frédéric Blanc; Arndt Vogel; Dmitry Komov; T.R. Jeffry Evans; Carlos López-López; Corina E Dutcus; Min Ren; Silvija Kraljevic; Toshiyuki Tamai; Masatoshi Kudo
• Keywords: Clinical endpoint; Lenvatinib; Progression-free survival; Tolerability

4001 Background: SOR is the only approved agent in uHCC and new options are needed. LEN, an inhibitor of vascular endothelial growth factor receptors 1‒3, fibroblast 1‒4, platelet derived receptor α, RET, KIT, showed activity a phase II trial. We report III trial LEN vs as first-line therapy for uHCC. Methods: In this randomized, open-label, noninferiority (NI) study, pts had uHCC, ≥ 1 measurable target lesion, Barcelona Clinic Liver Cancer stage B or C, Child-Pugh class A, ECOG PS ≤ 1, no prior systemic therapy. Pts were randomized 1:1 to (body weight 60 kg: 12 mg/day; < 8 mg/day) 400 mg twice daily. The primary endpoint was overall survival (OS). OS hazard ratio (HR) its 95% CI estimated with stratified Cox proportional model. predefined NI margin 1.08. Secondary efficacy endpoints progression-free (PFS), time progression (TTP) objective response rate (ORR) by modified RECIST. Type I error rates secondary controlled fixed sequence procedure at 2-sided α = 0.05 after claimed. Results: 954 enrolled (LEN: 478; SOR: 476). Efficacy outcomes shown table. A similar number both arms treatment-emergent adverse events (TEAEs). Most common TEAEs hypertension (42%), diarrhea (39%), decreased appetite (34%), (31%), fatigue (30%). Median (range) treatment duration 5.7 mos (0−35.0) 3.7 (0.1−38.7) SOR. 13% Of LEN-treated 9% SOR-treated discontinued due events. 33% 39% received second-line Conclusions: noninferior OS, achieves statistically significant clinically meaningful improvements PFS, TTP, ORR, first line consistent known safety profile. Clinical information: NCT01761266. [Table: see text]