A Randomized Study of Lenvatinib 18 mg vs 24 mg in Patients With Radioiodine-Refractory Differentiated Thyroid Cancer

Background Lenvatinib is a multikinase inhibitor approved to treat radioiodine-refractory differentiated thyroid cancer (RR-DTC) at a starting dose of 24 mg/day. This study explored, in a double-blinded fashion, whether a starting dose of 18 mg/day would provide comparable efficacy with reduced toxicity. Methods Patients with RR-DTC were randomized to lenvatinib 24 mg/day or 18 mg/day. The primary efficacy endpoint was objective response rate as of week 24 (ORRwk24); the odds ratio noninferiority margin was 0.4. The primary safety endpoint was frequency of grade >= 3 treatment-emergent adverse events (TEAEs) as of week 24. Tumors were assessed using RECIST v1.1. TEAEs were monitored and recorded. Results The ORRwk24 was 57.3% (95% CI 46.1, 68.5) in the lenvatinib 24-mg arm and 40.3% (95% CI 29.3, 51.2) in the lenvatinib 18-mg arm, with an odds ratio (18/24 mg) of 0.50 (95% CI 0.26, 0.96). As of week 24, the rates of TEAEs grade >= 3 were 61.3% in the lenvatinib 24-mg arm and 57.1% in the lenvatinib 18-mg arm, a difference of -4.2% (95% CI -19.8, 11.4). Conclusion A starting dose of lenvatinib 18 mg/day did not demonstrate noninferiority compared to a starting dose of 24 mg/day as assessed by ORRwk24 in patients with RR-DTC. The results represent a clinically meaningful difference in ORRwk24. The safety profile was comparable, with no clinically relevant difference between arms. These results support the continued use of the approved starting dose of lenvatinib 24 mg/day in patients with RR-DTC and adjusting the dose as necessary.

Automated summary

This study compared the efficacy and toxicity of lenvatinib starting at doses of 24 mg/day and 18 mg/day in patients with RR-DTC. The results showed that the objective response rate was 57.3% in the 24 mg/day arm and 40.3% in the 18 mg/day arm, indicating that the starting dose of 18 mg/day did not demonstrate noninferiority. However, there was no clinically relevant difference in the safety profile between the two arms.