Abstract
BACKGROUND: Lenvatinib is an approved first-line treatment for unresectable hepatocellular carcinoma (uHCC). We evaluated the safety and efficacy of lenvatinib versus sorafenib in patients with uHCC who deteriorated to Child-Pugh class B (CP-B) on treatment. METHODS: We retrospectively evaluated patients from REFLECT who deteriorated to CP-B versus those who remained Child-Pugh class A (CP-A) within 8 weeks after randomization. Best overall response and objective response rate (ORR) per modified Response Evaluation Criteria In Solid Tumors (mRECIST) were assessed from baseline. Progression-free survival (PFS) per mRECIST and overall survival (OS) were assessed beginning at week 8. RESULTS: Patients with CP-B versus CP-A classification receiving lenvatinib had ORRs of 28.3 and 42.9%, respectively; patients with CP-B versus CP-A classification receiving sorafenib had ORRs of 8.5 and 12.9%, respectively. Median PFS and OS (landmark analyses beginning at week 8) in patients receiving lenvatinib were 3.7 months [95% confidence interval (CI): 1.8-7.4] and 6.8 months (95% CI: 2.6-10.3) in the CP-B subgroup versus 6.5 months (95% CI: 5.6-7.4) and 13.3 months (95% CI: 11.6-16.1) in the CP-A subgroup, respectively. Median PFS and OS in patients receiving sorafenib were 0.5 months (95% CI: 0.1-3.6) and 4.5 months (95% CI: 2.9-6.1) in the CP-B subgroup versus 3.6 months (95% CI: 2.7-3.7) and 12.0 months (95% CI: 10.2-14.0) in the CP-A subgroup, respectively. The most common treatment-emergent adverse events in the lenvatinib cohort were hypertension (both subgroups) and decreased appetite (CP-B subgroup). CONCLUSION: Results suggest that patients with uHCC whose liver function deteriorates to CP-B after initiation of therapy may continue to receive lenvatinib. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01761266, https://clinicaltrials.gov/ct2/show/NCT01761266.