FDA Approval Summary: Cabozantinib for Differentiated Thyroid Cancer

Area of Science:

• Oncology
• Pharmacology
• Clinical Trials

Background:

• Differentiated thyroid cancer (DTC) can become refractory to radioactive iodine (RAI) and progress despite VEGFR-targeted therapy.
• Limited treatment options exist for patients with advanced or metastatic DTC that has progressed following prior therapies.
• Pediatric patients with DTC historically had fewer approved treatment options.

Purpose of the Study:

• To evaluate the efficacy and safety of cabozantinib in adult and pediatric patients with locally advanced or metastatic RAI-refractory DTC.
• To assess progression-free survival (PFS) and overall response rate (ORR) in patients treated with cabozantinib compared to placebo.
• To support the FDA approval of cabozantinib for this specific patient population.

Main Methods:

• A randomized, double-blind, placebo-controlled international trial (COSMIC-311) involving 258 patients.
• Patients received either oral cabozantinib (60 mg once daily) or placebo with best supportive care.
• Efficacy endpoints included PFS and ORR, assessed by blinded independent central review using RECIST 1.1 criteria.

Main Results:

• Median PFS was significantly longer in the cabozantinib arm (11.0 months) compared to the placebo arm (1.9 months), with a hazard ratio of 0.22.
• The study met its primary endpoint for PFS.
• The overall response rate (ORR) endpoint was not met. Hypocalcemia was identified as a new safety warning.

Conclusions:

• Cabozantinib demonstrates significant efficacy in improving progression-free survival for patients with advanced or metastatic RAI-refractory DTC who have progressed on prior VEGFR-targeted therapy.
• The drug's approval provides a new therapeutic option for this challenging patient group, including pediatric patients.
• Cabozantinib is the first therapy approved for RAI-refractory DTC patients who have progressed after prior treatment.