FDA Approves Cabozantinib for Locally Advanced or Metastatic DTC

On September 17, 2021, the FDA approved cabozantinib (Cabometyx, Exelixis, Inc.) for both adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that progressed following prior VEGFR-targeted therapy and are ineligible or refractory to radioactive iodine. 

The COSMIC-311 is a double-blind, placebo-controlled, multicenter clinical trial that evaluated efficacy in patients with locally advanced or metastatic DTC. Patients were randomized to receive either cabozantinib 60 mg orally once daily or placebo with the best supportive care until disease progression or intolerable toxicity.

The primary endpoint was 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 RECIST 1.1.

Study findings showed 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) for those who received a 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 events (AEs) were diarrhea, palmar-plantar erythrodysesthesia (PPE), fatigue, hypertension, and stomatitis with a warning for hypocalcemia.

The recommended single-agent cabozantinib dose is 60 mg once daily until disease progression or unacceptable toxicity for adult patients. For pediatric patients 12 years of age or older with BSA less than 1.2 m2, the recommended cabozantinib dose is 40 mg once daily until disease progression or unacceptable toxicity. —Alexa Stoia

Source: US Food and Drug Administration.FDA approves cabozantinib for differentiated thyroid cancer. September, 17, 2021. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cabozantinib-differentiated-thyroid-cancer?utm_medium=email&utm_source=govdelivery Accessed September 22, 2021.