Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2023

Lenvatinib vs sorafenib in the first-line treatment of patients with unresectable hepatocellular carcinoma (uHCC) and nonviral etiology: REFLECT post-hoc analysis (#216)

Ari David Baron 1 , Carlos López López 2 , Stephen Lam Chan 3 , Fabio Piscaglia 4 , Min Ren 5 , Kasey Estenson 5 , Chunyan Ma 6 , Arndt Vogel 7 , Pierre Gholam 8
  1. Sutter/California Pacific Medical Center, San Francisco, CA, USA
  2. Marqués de Valdecilla University Hospital, IDIVAL, Santander, Spain
  3. The Chinese University of Hong Kong, Shatin, Hong Kong
  4. IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
  5. Eisai Inc., Nutley, NJ, USA
  6. Eisai Australia Pty Ltd, Melbourne, Victoria, Australia
  7. Hannover Medical School, Hannover, Germany
  8. Case Western Reserve University School of Medicine, Cleveland, OH, USA

Background: The randomized phase 3 REFLECT trial (NCT01761266) demonstrated that lenvatinib was non-inferior to sorafenib in OS in 1L uHCC (HR, 0.92; 95% CI, 0.79-1.06). PFS (HR, 0.64; 95% CI, 0.55-0.75; p<0.0001) and ORR (odds ratio, 5.01; 95% CI 3.59-7.01; p<0.0001) by IIR per mRECIST favored lenvatinib versus sorafenib. Recent data suggest that viral/nonviral etiology may impact treatment outcomes. This post-hoc analysis evaluated patients with nonviral etiology in REFLECT.

Methods: In REFLECT, 1L uHCC patients  were randomized to lenvatinib (12 mg/day, bodyweight ≥60 kg; 8 mg/day, bodyweight <60 kg) or sorafenib (400 mg twice-daily) in 28-day cycles. This post-hoc analysis included patients without hepatitis B/C (medical history) who were randomized to receive lenvatinib or sorafenib. PFS, ORR (by IIR per mRECIST), and OS were analyzed.

Results: 127 Patients randomized to lenvatinib and 108 patients randomized to sorafenib had nonviral etiology. Among these patients, mOS was 13.8 months (95% CI, 10.5-18.7) with lenvatinib and 13.9 months (95% CI, 11.7-17.5) with sorafenib (HR, 1.03; 95% CI, 0.75-1.43). mPFS was 7.4 months (95% CI, 5.5-8.7) in the lenvatinib arm and 4.0 months (95% CI, 3.6-5.5) in the sorafenib arm (HR, 0.60; 95% CI, 0.42-0.87). ORR was 39.4% (95% CI 30.9-47.9) in the lenvatinib arm and 20.4% (95% CI 12.8-28.0) in the sorafenib arm. Fewer (n=34 [26.8%]) patients with nonviral etiology randomized to lenvatinib received anticancer medication during survival follow-up than those randomized to sorafenib (n=46 [42.6%]).

Conclusion: In this post-hoc analysis, OS, PFS, and ORR in patients randomized to lenvatinib with nonviral etiology were consistent with the overall population of patients randomized to lenvatinib. These results, along with the results of the primary analysis of REFLECT, demonstrate the efficacy of lenvatinib regardless of etiology in uHCC, and support lenvatinib as a standard-of-care-option for patients with 1L uHCC. Prospective trials by etiology are still needed.

  1. © 2023 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2023 ASCO Annual Meeting. All rights reserved.