On September 17, 2021, the U.S. Food and Drug Administration (FDA) approved cabozantinib (Cabometyx®) for adult and pediatric patients aged 12 years and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior vascular endothelial growth factor (VEGFR)-targeted therapy and who are ineligible for or refractory to radioactive iodine treatment.
Efficacy was evaluated in COSMIC-311, a randomized (2:1), double-blind, placebo-controlled, multicenter clinical trial (NCT03690388) in patients with locally advanced or metastatic DTC that had progressed following prior VEGFR-targeted therapy and were ineligible or refractory to radioactive iodine. Patients were randomized to receive either cabozantinib 60 mg orally once daily or placebo with best supportive care until they experienced disease progression or intolerable toxicity.
The primary efficacy outcome measures were progression-free survival (PFS) in the intent-to-treat population and overall response rate (ORR) in the first 100 randomized patients, assessed by a blinded independent radiology review committee per Response Evaluation Criteria in Solid Tumors 1.1. Cabozantinib significantly reduced the risk of disease progression or death versus placebo (p < 0.0001). The median PFS was 11.0 months (95% CI = 7.4, 13.8) in the cabozantinib arm, compared to 1.9 months (95% CI = 1.9, 3.7) in the placebo arm. The ORR was 18% (95% CI = 10%, 29%) and 0% (95% CI = 0%, 11%) in the cabozantinib and placebo arms, respectively.
The most common adverse reactions (≥ 25%) were diarrhea, palmar-plantar erythrodysesthesia, fatigue, hypertension, and stomatitis. The new indication adds a warning for hypocalcemia.
The recommended dose for cabozantinib as a single agent is 60 mg once daily until patients experience disease progression or unacceptable toxicity. The recommended cabozantinib dose in pediatric patients (aged 12 years and older with a body surface area less than 1.2 m2) is 40 mg once daily until they experience disease progression or unacceptable toxicity.
The review used Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. FDA approved the application two months ahead of the goal date. It was granted priority review, breakthrough designation, and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact the Office of Oncology Excellence’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.