On 17 September 2021, the US Food and Drug Administration (FDA) approved cabozantinib (Cabometyx, Exelixis, Inc.) for adult and paediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior vascular endothelial growth factor receptor (VEGFR)-targeted therapy and who are ineligible or refractory to radioactive iodine.

Efficacy was evaluated in COSMIC-311, a randomised (2:1), double-blind, placebo-controlled, multicentre clinical study (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 randomised to receive either cabozantinib 60 mg orally once daily or placebo with best supportive care until 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 randomised patients, assessed by a blinded independent radiology review committee per RECIST v1.1.

Cabozantinib significantly reduced the risk of disease progression or death versus placebo (p < 0.0001). The median PFS was 11.0 months (95% confidence interval [CI] 7.4, 13.8) in the cabozantinib arm compared to 1.9 months (95% CI 1.9, 3.7) for those receiving placebo.

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 diarrhoea, palmar-plantar erythrodysesthesia, fatigue, hypertension, and stomatitis. A warning was added for hypocalcaemia.

The recommended single-agent cabozantinib dose is 60 mg once daily until disease progression or unacceptable toxicity. The recommended cabozantinib dose in paediatric patients (12 years of age and older with body surface area less than 1.2 m2) is 40 mg once daily until disease progression or unacceptable toxicity.

Full prescribing information for Cabometyx is available here.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 2 months ahead of the FDA goal date.

This application was granted priority review, breakthrough designation and orphan drug designation.

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