Document Type

Article

Publication Date

2-17-2022

Comments

This article is the author’s final published version in The Journal of clinical endocrinology and metabolism, Volume 107, Issue 3, February 2022, Pages 776 - 787.

The published version is available at https://doi.org/10.1210/clinem/dgab731. Copyright © Brose et al.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT02702388.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

PubMed ID

34664662

Language

English

Included in

Oncology Commons

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