Phase III trial of lenvatinib (LEN) vs sorafenib (SOR) in first-line treatment of patients (pts) with unresectable hepatocellular carcinoma (uHCC).
-
- Ann-Lii Cheng
- National Taiwan University Hospital, Taipei, Taiwan;
-
- Richard S. Finn
- David Geffen School of Medicine at University of California Los Angeles, Santa Monica, CA;
-
- Shukui Qin
- Nanjing Bayi Hospital, Nanjing, China;
-
- Kwang-Hyub Han
- Severance Hospital, Yonsei University, Seoul, South Korea;
-
- Kenji Ikeda
- Toranomon Hospital, Tokyo, Japan;
-
- Fabio Piscaglia
- Azienda Ospedaliera Di Bologna, Bologna, Italy;
-
- Ari David Baron
- California Pacific Medical Center Research Institute, San Francisco, CA;
-
- Joong-Won Park
- National Cancer Center Korea, Goyang-Si, South Korea;
-
- Guohong Han
- Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China;
-
- Jacek Jassem
- Medical University of Gdańsk, Department of Oncology and Radiotherapy, Gdańsk, Poland;
-
- Jean-Frédéric Blanc
- Service d’Hépato-Gastroentérologie et d’Oncologie Digestive, Groupe Hospitalier Saint André, Bordeaux, France;
-
- Arndt Vogel
- Hannover Medical School, Hannover, Germany;
-
- Dmitry Komov
- N. N. Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, Russia;
-
- T.R. Jeffry Evans
- University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom;
-
- Carlos López-López
- Marqués de Valdecilla University Hospital, Santander, Spain;
-
- Corina E Dutcus
- Eisai Co., Ltd., Woodcliff Lake, NJ;
-
- Min Ren
- Eisai Co., Ltd., Woodcliff Lake, NJ;
-
- Silvija Kraljevic
- Eisai Co., Ltd., Hatfield, United Kingdom;
-
- Toshiyuki Tamai
- Eisai Co., Ltd., Woodcliff Lake, NJ;
-
- Masatoshi Kudo
- Kindai University Faculty of Medicine, Osaka, Japan;
抄録
<jats:p> 4001 </jats:p><jats:p> 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. [Table: see text] </jats:p>
収録刊行物
-
- Journal of Clinical Oncology
-
Journal of Clinical Oncology 35 (15_suppl), 4001-4001, 2017-05-20
American Society of Clinical Oncology (ASCO)