On September 17, 2021, the FDA approved cabozantinib (Cabometyx; Exelixis, Inc.) for the treatment of adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who is radioactive iodine (RAI)-refractory or ineligible. This is the first approval for patients with RAI-refractory locally advanced or metastatic DTC who have progressed following prior therapy and the first approval in pediatric patients with DTC. The approval was based on data from COSMIC-311 (Study XL184-311, NCT03690388), an international, randomized, double-blind trial in which patients with locally advanced or metastatic RAI-refractory DTC that progressed during or following treatment with at least one VEGF-targeting tyrosine kinase inhibitor were treated with either cabozantinib 60 mg orally once daily (N=170) or placebo with best supportive care (N=88). The major efficacy outcome measures were progression-free survival (PFS) and overall response rate (ORR) by blinded independent central review under RECIST 1.1. The median PFS was 11.0 months [95% CI, 7.4–13.8] in the cabozantinib arm compared with 1.9 months (95% CI, 1.9–3.7) in the control arm, with an HR of 0.22 (95% CI, 0.15–0.31). The endpoint of ORR was not met. No new safety signals were detected except hypocalcemia, which was added as a warning in the product labeling.
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