As reported in the Journal of Clinical Oncology by Lori J. Wirth, MD, and colleagues, a phase II trial of lenvatinib in patients with anaplastic thyroid cancer was stopped for futility after an interim analysis.
Lori J. Wirth, MD
Study Details
In the international multicenter trial, 34 patients received lenvatinib at 24 mg once daily. Patients who had prior surgery or radiation ≥ 2 weeks before the first dose of lenvatinib could be enrolled, and prior neoadjuvant, adjuvant, or palliative chemotherapy—but not tyrosine kinase inhibitor therapy—was permitted.
An interim analysis was conducted after enrollment of the first 20 patients, with a confirmed objective response rate of 15% constituting the futility threshold. The primary endpoints were investigator-assessed objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 and safety.
Key Findings
At the interim analysis, no confirmed objective responses were observed in 20 patients (response rate = 0%). An unconfirmed partial response was observed in one patient (5%, 95% confidence interval [CI] = 0.1%–24.9%). The study was thus halted for futility.
Among all 34 patients, a confirmed partial response was observed in one patient (2.9%, 95% CI = 0.1%–15.3%), with response maintained for 4.1 months. An additional 17 patients (50%) had stable disease. Two patients had > 30% reduction in total target lesion size, but response could not be confirmed due to progressive disease. Tumor shrinkage was observed in 16 of 28 evaluable patients. The disease control and clinical benefit rates were 52.9% (95% CI = 35.1%–70.2%) and 8.8% (95% CI = 1.9%–23.7%), respectively.
Among all patients, median progression-free survival was 2.6 months (95% CI = 1.4–2.8 months) and median overall survival was 3.2 months (95% CI = 2.8–8.2 months).
The most common treatment-related adverse events were hypertension (56%), decreased appetite (29%), fatigue (29%), and stomatitis (29%). Grade ≥ 3 treatment-related adverse events occurred in 62% of patients, with the most common being hypertension (24%) and asthenia (9%). No major treatment-related bleeding events were observed, and no treatment-related deaths were reported.
The investigators concluded, “The safety profile of lenvatinib in anaplastic thyroid cancer was manageable, and many adverse events were attributable to the progression of anaplastic thyroid cancer. The results suggest that lenvatinib monotherapy may not be an effective treatment for anaplastic thyroid cancer; further investigation may be warranted.”
Dr. Wirth, of Harvard Medical School, Massachusetts General Hospital, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Eisai Inc and Merck Sharp & Dohme Corp, a subsidiary of Merck & Co Inc. For full disclosures of the study authors, visit ascopubs.org.
