Lenvatinib Not Effective for Patients With Anaplastic Thyroid Cancer

Findings from an open-label, multicenter, phase 2 trial suggest that lenvatinib monotherapy may not be an effective treatment for anaplastic thyroid cancer (ATC; J Clin Oncol. 2021 Jul 20;39(21):2359-2366.).

“Anaplastic thyroid cancer, 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,” explained Lori Wirth, MD, Harvard Medical School, Massachusetts General Hospital, Boston, and colleagues.

Lenvatinib is US FDA-approved for radioiodine-refractory differentiated thyroid cancer that previously showed activity in a small study of patients with ATC. With this in mind, Dr Wirth and her team set out to further evaluate lenvatinib for ATC.

The international, single-arm trial included patients with ATC who had ≥ 1 measurable target lesion; patients received 24mg of lenvatinib once daily.

The primary end points were objective response rate (ORR) by investigator assessment per RECIST v1.1 and safety. Secondary end points included progression-free survival (PFS) and overall survival (OS).

Upon interim analyses, the study ceased due to the minimum ORR threshold of 15% not being reached. In the full analysis set of 34 patients, one achieved a partial response (ORR, 2.9%; 95% CI, 0.1 to 15.3). Furthermore, over half of the evaluable patients experienced tumor shrinkage, while three saw a tumor reduction of >30%.

The median PFS and OS were 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), respectively.

The most common treatment-related adverse events (AEs) included hypertension (56%), decreased appetite (29%), fatigue (29%), and stomatitis (29%). There were no grade 5 treatment-related AEs.

“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” concluded Dr Wirth et al. —Alexandra Graziano