2017 ASCO Annual Meeting!
Session: Gastrointestinal (Noncolorectal) Cancer
Type: Oral Abstract Session
Time: Sunday June 4, 8:00 AM to 11:00 AM
Location: Hall D2
Phase III trial of lenvatinib (LEN) vs sorafenib (SOR) in first-line treatment of patients (pts) with unresectable hepatocellular carcinoma (uHCC).
Gastrointestinal (Noncolorectal) Cancer
2017 ASCO Annual Meeting
J Clin Oncol 35, 2017 (suppl; abstr 4001)
Author(s): 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; National Taiwan University Hospital, Taipei, Taiwan; David Geffen School of Medicine at University of California Los Angeles, Santa Monica, CA; Nanjing Bayi Hospital, Nanjing, China; Severance Hospital, Yonsei University, Seoul, South Korea; Toranomon Hospital, Tokyo, Japan; Azienda Ospedaliera Di Bologna, Bologna, Italy; California Pacific Medical Center Research Institute, San Francisco, CA; National Cancer Center Korea, Goyang-Si, South Korea; Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China; Medical University of Gdańsk, Department of Oncology and Radiotherapy, Gdańsk, Poland; Service d’Hépato-Gastroentérologie et d’Oncologie Digestive, Groupe Hospitalier Saint André, Bordeaux, France; Hannover Medical School, Hannover, Germany; N. N. Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, Russia; University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom; Marqués de Valdecilla University Hospital, Santander, Spain; Eisai Co., Ltd., Woodcliff Lake, NJ; Eisai Co., Ltd., Hatfield, United Kingdom; Kindai University Faculty of Medicine, Osaka, Japan
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 growth factor receptors 1‒4, platelet derived growth factor receptor α, RET, and KIT, showed activity in uHCC in a phase II trial. We report a phase III trial of LEN vs SOR 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, and no prior systemic therapy. Pts were randomized 1:1 to LEN (body weight ≥ 60 kg: 12 mg/day; < 60 kg: 8 mg/day) or SOR 400 mg twice daily. The primary endpoint was overall survival (OS). The OS hazard ratio (HR) and its 95% CI were estimated with a stratified Cox proportional hazard model. The predefined NI margin was 1.08. Secondary efficacy endpoints were progression-free survival (PFS), time to progression (TTP) and objective response rate (ORR) by modified RECIST. Type I error rates for secondary efficacy endpoints were controlled with a fixed sequence procedure at 2-sided α = 0.05 after OS NI was claimed. Results: 954 Pts enrolled (LEN: 478; SOR: 476). Efficacy outcomes are shown in the table. A similar number of pts in both arms had treatment-emergent adverse events (TEAEs). Most common LEN TEAEs were hypertension (42%), diarrhea (39%), decreased appetite (34%), decreased weight (31%), and fatigue (30%). Median (range) treatment duration was 5.7 mos (0−35.0) for LEN and 3.7 mos (0.1−38.7) for SOR. 13% Of LEN-treated and 9% of SOR-treated pts discontinued due to adverse events. 33% Of LEN-treated and 39% of SOR-treated pts received second-line therapy. Conclusions: LEN is noninferior in OS, and achieves statistically significant and clinically meaningful improvements in PFS, TTP, and ORR, as first line therapy for uHCC. TEAEs were consistent with the known LEN safety profile. Clinical trial information: NCT01761266
|Median OS, mos (95% CI)||13.6 (12.1−14.9)||12.3 (10.4−13.9)||0.92 (0.79−1.06)|
|Median PFS, mos (95% CI)*||7.4 (6.9−8.8)||3.7 (3.6−4.6)||0.66 (0.57−0.77)|
|Median TTP, mos (95% CI)*||8.9 (7.4−9.2)||3.7 (3.6−5.4)||0.63 (0.53−0.73)|
|ORR, n (%)*||115 (24)||44 (9)|