Lenvatinib monotherapy may not be an effective treatment for patients with anaplastic thyroid cancer (ATC), investigators reported in the Journal of Clinical Oncology.
In a phase 2 trial (ClinicalTrials.gov Identifier: NCT02657369), lenvatinib produced an objective response rate (ORR) of about 3%. The median progression-free survival (PFS) and overall survival (OS) were both around 3 months.
The open-label, international study enrolled patients with ATC who had at least 1 measurable target lesion. They received lenvatinib at 24 mg once daily.
Among the 34 enrolled and treated patients, 47% were older than 65 years of age, 62% were women, and 79% were White. A majority of patients (65%) had both locoregional and distant metastatic disease, and 71% had received 1 or more prior anticancer therapies.
The primary efficacy endpoint was confirmed ORR. One patient achieved a partial response, for an ORR of 2.9%. The study was closed to enrollment after the first interim analysis because the prespecified ORR threshold of 15% was not met.
There were 28 patients who had tumor shrinkage, and 3 had a greater than 30% reduction in total target lesion size from baseline to postbaseline nadir. The disease control rate was 52.9%, and the clinical benefit rate was 8.8%.
The median PFS was 2.6 months, and the median OS was 3.2 months. The median follow-up time for OS was 15.3 months.
The investigators noted that they did not obtain patients’ BRAF mutation status for this study, and BRAF-mutated patients should be treated with BRAF-targeted therapies.
All 34 patients had treatment-emergent adverse events (TEAEs). TEAEs led to 14 deaths within 28 days of the last dose, but none of these events was considered related to treatment.
Grade 5 TEAEs included dysphagia (n = 1), septic shock (n = 1), hypoxia (n = 1), and malignant neoplasm progression (n = 10). One patient had 3 grade 5 TEAEs — cardiopulmonary failure, renal failure, and pulmonary edema.
Treatment-related adverse events (TRAEs) occurred in 94% of patients, and the most common were hypertension (56%), decreased appetite (29%), fatigue (29%), and stomatitis (29%). Grade 3 or higher TRAEs occurred in 62% of patients, with hypertension (24%) being the most common.
The investigators concluded that the safety profile of lenvatinib was manageable, as many adverse events were attributable to disease progression. However, lenvatinib monotherapy may not be an effective treatment for ATC.
“We hope that data from this study will provide useful information for future studies in patients with ATC, particularly the single-arm studies investigating lenvatinib in combination with other anticancer agents,” the study authors wrote.
Disclosures: This research was supported by Eisai Inc and Merck Sharp & Dohme Corp. Some of the study authors declared affiliations with pharmaceutical companies. Please see the original reference for a full list of disclosures.
Wirth LJ, Brose MS, Sherman EJ, et al. Open-label, single-arm, multicenter, phase II trial of lenvatinib for the treatment of patients with anaplastic thyroid cancer. J Clin Oncol. Published online May 7, 2021. doi: 10.1200/JCO.20.03093