Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2017

Phase 3 trial of lenvatinib (LEN) vs sorafenib (SOR) in first-line treatment of patients (pts) with unresectable hepatocellular carcinoma (uHCC) (#153)

Ann-Lii Cheng 1 , Richard S Finn 2 , Shukui Qin 3 , Kwan-Hyub Han 4 , Kenji Ikeda 5 , Fabio Piscaglia 6 , Ari Baron 7 , Joong-Won Park 8 , Guohong Han 9 , Jacek Jassem 10 , Jean Frederic Blanc 11 , Arndt Vogel 12 , Dmitry Komov 13 , TR Jeffry Evans 14 , Carlos Lopez 15 , Corina Dutcus 16 , Min Ren 16 , Silvija Kraljevic 17 , Toshiyuki Tamai 16 , John Bower 18 , Masatoshi Kudo 19
  1. National Taiwan University Hospital, Taipei, Taiwan
  2. Geffen School of Medicine, UCLA Medical Center, Santa Monica, CA, USA
  3. Nanjing Bayi Hospital, Nanjing, Jiangsu, China
  4. Severance Hospital, Yonsei University, Seoul, Korea
  5. Toranomon Hospital, Tokyo, Japan
  6. University of Bologna, Bologna, Italy
  7. California Pacific Medical Center Research Institute, San Francisco, CA, USA
  8. National Cancer Center Korea, Goyana-si, Korea
  9. Xijing Hospital, Fourth Military Medical University, Xi'an, China
  10. Medical University of Gdansk, Gdansk, Poland
  11. University of Bordeaux, Bordeaux, France
  12. Hannover Medical School, Hannover, Germany
  13. N.N Blokhin Cancer Research Center, Moscow, Russia
  14. University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, UK
  15. Marques de Valdecilla, University of Hospital, Santander, Spain
  16. Eisai Inc., Woodcliff Lake, NJ, USA
  17. Eisai Ltd, Hatfield, UK
  18. Eisai Australia Pty Ltd, Melbourne, VIC, Australia
  19. Kindai University Faculty of Medicine, Osaka-Sayama, Japan


SOR is the only approved agent in uHCC, necessitating new options. LEN, an inhibitor of VEGFR1‒3, FGFR1‒4, PDGFRα, RET, and KIT, showed activity in uHCC in a phase 2 trial. We report a phase 3 trial of LEN vs SOR as first-line uHCC treatment.


In this randomized, open-label, noninferiority study, pts had uHCC, ≥1 measurable target lesion, BCLC stage B or C, Child-Pugh A, ECOG PS≤1, and no prior systemic therapy. Pts were randomized 1:1 to LEN (weight ≥60 kg: 12 mg/day; <60 kg: 8 mg/day) or SOR 400 mg twice daily. Primary endpoint was OS. OS HR and its 95% CI were estimated with a stratified Cox proportional hazard model. The predefined noninferiority margin was 1.08. Secondary efficacy endpoints were PFS, TTP, and ORR by mRECIST. Type I error rates for secondary efficacy endpoints were controlled with a fixed sequence procedure at 2-sided α=0.05 after claiming OS noninferiority.


954 Pts enrolled (LEN: 478; SOR: 476). Efficacy outcomes appear in the table. TEAE incidence was similar in both arms, with the most common being 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.


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.




HR (95% CI)

Median OS, mos



0.92 (0.79−1.06)

Median PFS, mos*



0.66 (0.57−0.77)

Median TTP, mos*



0.63 (0.53−0.73)

ORR, n (%)*


44 (9)