FDA Grants Breakthrough Therapy to Cabozantinib to Treat Patients with Differentiated Thyroid Cancer

Exelixis recently announced that cabozantinib received a breakthrough therapy designation from the FDA based on data from the COSMIC-311 trial for the treatment of differentiated thyroid cancer.

In February, the FDA granted breakthrough therapy designation to cabozantinib (Cabometyx) to treat patients with radioactive iodine–refractory differentiated thyroid cancer who progressed after previously receiving therapy, according to a press release from Exelixis.1

“Receiving Breakthrough Therapy Designation is a testament to both the urgent need for effective treatments for patients with differentiated thyroid cancer who progressed after prior therapy and the promising data demonstrating cabozantinib significantly improved progression-free survival for these patients,” Gisela Schwab, MD, president of Product Development and Medical Affairs and chief medical officer of Exelixis, said in a press release.

The multicenter, randomized, phase 3 COSMIC-311 trial (NCT03690388) demonstrated clinically significant evidence when using cabozantinib to treat patients with radioactive iodine–refractory differentiated thyroid cancer who progressed after receiving prior VEGFR-targeted therapies.

At an interim analysis, the trial met its co-primary end point by demonstrating a 78% reduction in the risk of disease progression or death versus placebo for this cohort of patients (HR, 0.22; 96% CI, 0.13-0.36; P < .0001).

Based on these results, the independent data monitoring committee recommended that trial enrollment be stopped and to unblind patients and sites.2

“Considering the poor prognosis and lack of progress in the treatment of differentiated thyroid cancer following anti-VEGFR therapy, a significant improvement in progression-free survival is a long-awaited clinical advance,” Marcia S. Brose, MD, PhD, full professor of Otorhinolaryngology: Head and Neck Surgery and director of the Center for Rare Cancers and Personalized Therapy at the Abramson Cancer Center of the University of Pennsylvania, and principal investigator of the trial, said in a press release.

The COSMIC-311 trial aimed to enroll 300 patients across 150 centers internationally. The population was randomized 2:1 to receive either 60 mg cabozantinib or placebo once daily. The safety profile was consistent with that of other data examining cabozantinib.

The co-primary end points of the phase 3 trial are progression-free survival and objective response rate.

“We look forward to submitting our regulatory application in 2021 and to working closely with the FDA during the review process, with the goal of bringing cabozantinib to this patient population with a high unmet medical need for whom there is currently no available standard of care,” explained Schwab.

The FDA grants breakthrough therapy designation to “expedite the development and review of drugs that are intended to treat serious or life threatening diseases.” For a potential drug to qualify for this designation, the clinical evidence must show substantial improvement for at least 1 clinically significance end point with the drug compared to existing therapeutic options.


1. Exelixis Announces Breakthrough Therapy Designation Granted to Cabozantinib for the Treatment of Patients with Previously Treated Radioactive Iodine-Refractory Differentiated Thyroid Cancer. Exelixis. Published February 25, 2021. Accessed March 10, 2021. https://ir.exelixis.com/news-releases/news-release-details/exelixis-announces-breakthrough-therapy-designation-granted

2. Exelixis announces cabozantinib significantly improved progression-free survival in COSMIC-311 phase 3 pivotal trial in patients with previously treated radioiodine-refractory differentiated thyroid cancer. News release. December 21, 2020. Accessed March 17, 2021. https://ir.exelixis.com/news-releases/news-release-details/exelixis-announces-cabozantinib-significantly-improved