Lenvatinib versus Sorafenib in First-Line Treatment of Older Patients with Unresectable Hepatocellular Carcinoma: A Subgroup Analysis of the REFLECT Trial
In brief
Lenvatinib doubles response rate and adds two months PFS for patients 65+
In the REFLECT trial subgroup of 401 patients aged 65 or older with unresectable liver cancer, lenvatinib achieved a 43% response rate versus 15% with sorafenib and extended median progression-free survival to 7.4 months versus 5.4 months. Overall survival was similar, and safety was comparable, supporting lenvatinib as a viable first-line option for older adults.
- Journal
- Liver cancer (Q1)
- Published
- 4 July 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Masatoshi Kudo, Arndt Vogel, Thomas R Jeffry Evans, Yuk Ting Ma, Bruno Daniele, Ari David Baron, et al.
- PMID
- 42677015
- DOI
- 10.1159/000553375
Why clinicians should know about it
- Picked for Histology (top studies of the week, 6 September 2026): High-quality evidence in a top journal
- Picked for Oncology and Radiation Oncology (top studies of the week, 6 September 2026): Lenvatinib shows improved PFS vs sorafenib in older HCC patients
Abstract
INTRODUCTION: In the open-label, phase 3 REFLECT trial, lenvatinib had noninferior overall survival (OS) to sorafenib, as well as improved progression-free survival (PFS) and objective response rate (ORR) in patients with unresectable hepatocellular carcinoma (uHCC). We report post hoc safety and efficacy in older patients. METHODS: In REFLECT (NCT01761266), patients with histologically/cytologically confirmed uHCC were randomly assigned 1:1 to lenvatinib (12 mg/day [bodyweight ≥60 kg] or 8 mg/day [bodyweight <60 kg]) or sorafenib 400 mg twice daily in 28-day cycles. In this analysis, OS, PFS, ORR, and safety were evaluated in patients aged ≥65 and ≥75 years. Efficacy was evaluated per modified Response Evaluation Criteria in Solid Tumors by masked independent imaging review. RESULTS: By data cutoff (November 13, 2016), 401 patients (208 receiving lenvatinib, 193 receiving sorafenib) were aged ≥65 years; of them, 125 (58 receiving lenvatinib, 67 receiving sorafenib) were aged ≥75 years. In the age ≥65 group, median OS was 14.6 months (95% CI: 13.0-18.7) in the lenvatinib arm and 13.4 months (95% CI: 11.6-16.3) in the sorafenib arm (hazard ratio [HR]: 0.844; 95% CI: 0.664-1.074); the OS HR was 0.807 (95% CI: 0.634-1.028) after adjusting for baseline alpha-fetoprotein. Median PFS was 7.4 months (95% CI: 5.6-9.1) with lenvatinib and 5.4 months (95% CI: 3.6-5.5) with sorafenib (HR: 0.571; 95% CI: 0.432-0.755). ORRs were 42.8% (95% CI: 36.1-49.5) with lenvatinib and 14.5% (95% CI: 9.5-19.5) with sorafenib. The most frequent treatment-emergent adverse events (TEAEs) were hypertension (47.3%) in the lenvatinib arm and palmar-plantar erythrodysesthesia syndrome (50.8%) in the sorafenib arm. The incidence of grade ≥3 TEAEs was 82.1% and 72.5% in the lenvatinib and sorafenib arm, respectively. Similar results were observed in patients aged ≥75 years. CONCLUSION: Consistent with the overall REFLECT population, older patients in the lenvatinib arm generally showed improved efficacy versus the sorafenib arm, supporting lenvatinib as an option for older patients with uHCC.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.