Open-Label, Single-Arm, Multicenter, Phase II Trial of Lenvatinib for the Treatment of Patients With Anaplastic
Lori J Wirth1, Marcia S Brose2, Eric J Sherman3
1Harvard Medical School, Massachusetts General Hospital, Boston, MA.
Purpose:
Anaplastic thyroid cancer (ATC), an aggressive malignancy, is associated with a poor prognosis and an unmet need for effective treatment, especially for patients without BRAF mutations or NTRK or RET fusions. Lenvatinib is US Food and Drug Administration-approved for radioiodine-refractory differentiated thyroid cancer and has previously demonstrated activity in a small study of patients with ATC (n = 17). We aimed to further evaluate lenvatinib in ATC.
Methods:
This open-label, multicenter, international, phase II study enrolled patients with ATC, who had ≥ 1 measurable target lesion, to receive lenvatinib 24 mg once daily. The primary end points were objective response rate (ORR) by investigator assessment per RECIST v1.1 and safety. Responses were confirmed ≥ 4 weeks after the initial response. Additional end points included progression-free survival and overall survival (OS).
Results:
The study was halted for futility as the minimum ORR threshold of 15% was not met upon interim analysis. The interim analysis set included the first 20 patients. The full analysis set includes all 34 enrolled and treated patients. In the full analysis set, one patient achieved a partial response (ORR, 2.9%; 95% CI, 0.1 to 15.3). More than half of the evaluable patients experienced tumor shrinkage; three patients experienced a > 30% tumor reduction. The median progression-free survival was 2.6 months (95% CI, 1.4 to 2.8); the median overall survival was 3.2 months (95% CI, 2.8 to 8.2). The most common treatment-related adverse events (AEs) were hypertension (56%), decreased appetite (29%), fatigue (29%), and stomatitis (29%). No major treatment-related bleeding events or grade 5 treatment-related AEs occurred.
Conclusion:
The safety profile of lenvatinib in ATC was manageable, and many AEs were attributable to the progression of ATC. The results suggest that lenvatinib monotherapy may not be an effective treatment for ATC; further investigation may be warranted.
Insights
Lenvatinib monotherapy showed limited efficacy in anaplastic thyroid cancer (ATC), with an objective response rate below the target threshold. The study was halted for futility, suggesting lenvatinib may not be an effective treatment for ATC.
Area of Science:
- Oncology
- Thyroid Cancer Research
- Pharmacological Studies
Background:
- Anaplastic thyroid cancer (ATC) is an aggressive malignancy with a poor prognosis and limited effective treatment options.
- Targeted therapies are needed, particularly for patients lacking specific mutations like BRAF or fusions such as NTRK or RET.
- Lenvatinib, approved for differentiated thyroid cancer, has shown prior activity in a small ATC cohort.
Purpose of the Study:
- To evaluate the efficacy and safety of lenvatinib in patients with anaplastic thyroid cancer (ATC).
- To determine the objective response rate (ORR) of lenvatinib in this patient population.
- To assess progression-free survival (PFS) and overall survival (OS) as secondary endpoints.
Main Methods:
- An open-label, multicenter, international, phase II study was conducted.
- Patients with ATC and measurable disease received lenvatinib 24 mg once daily.
- Primary endpoints included investigator-assessed ORR per RECIST v1.1 and safety; secondary endpoints were PFS and OS.
Main Results:
- The study was halted for futility due to an interim objective response rate (ORR) below the 15% threshold.
- In the full analysis set (n=34), one patient achieved a partial response, resulting in an ORR of 2.9%.
- Median PFS was 2.6 months and median OS was 3.2 months; common adverse events included hypertension and decreased appetite.
Conclusions:
- Lenvatinib monotherapy demonstrated limited efficacy in anaplastic thyroid cancer (ATC).
- The observed ORR did not meet the predefined threshold, leading to study discontinuation for futility.
- While the safety profile was manageable, lenvatinib monotherapy may not be a viable treatment strategy for ATC.
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