{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T16:19:17Z","timestamp":1788193157975,"version":"build-2803163510"},"reference-count":25,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver Cancer"],"abstract":"<jats:p>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 \u226560 kg] or 8 mg\/day [bodyweight &lt;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 \u226565 and \u226575 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 \u226565 years; of them, 125 (58 receiving lenvatinib, 67 receiving sorafenib) were aged \u226575 years. In the age \u226565 group, median OS was 14.6 months (95% CI: 13.0\u221218.7) in the lenvatinib arm and 13.4 months (95% CI: 11.6\u221216.3) in the sorafenib arm (hazard ratio [HR]: 0.844; 95% CI: 0.664\u22121.074); the OS HR was 0.807 (95% CI: 0.634\u22121.028) after adjusting for baseline alpha-fetoprotein. Median PFS was 7.4 months (95% CI: 5.6\u22129.1) with lenvatinib and 5.4 months (95% CI: 3.6\u22125.5) with sorafenib (HR: 0.571; 95% CI: 0.432\u22120.755). ORRs were 42.8% (95% CI: 36.1\u221249.5) with lenvatinib and 14.5% (95% CI: 9.5\u221219.5) 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 \u22653 TEAEs was 82.1% and 72.5% in the lenvatinib and sorafenib arm, respectively. Similar results were observed in patients aged \u226575 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.<\/jats:p>","DOI":"10.1159\/000553375","type":"journal-article","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T16:00:40Z","timestamp":1783180840000},"page":"1-14","source":"Crossref","is-referenced-by-count":0,"title":["Lenvatinib versus Sorafenib in First-Line Treatment of Older Patients with Unresectable Hepatocellular Carcinoma: A Subgroup Analysis of the REFLECT Trial"],"prefix":"10.1159","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4102-3474","authenticated-orcid":false,"given":"Masatoshi","family":"Kudo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arndt","family":"Vogel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R. 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