FDA Approves Cabozantinib for Radioactive Iodine–Refractory Differentiated Thyroid Cancer


Findings from the phase 3 COSMIC-311 trial led to the approval of cabozantinib in patients with radioactive iodine–refractory locally advanced or metastatic differentiated thyroid cancer.

Cabozantinib (Cabometyx) has been approved by the FDA for adult and pediatric patients aged 12 years or older with locally advanced or metastatic differentiated thyroid cancer (DTC) who have experienced progression following treatment with VEGFR targeted therapy and whose disease is refractory to radioactive iodine, according to a press release from drug developer Exelixis.1

The approval was based on the results of the pivotal phase 3 COSMIC-311 trial (NCT03690388) which examined the agent vs placebo in patients with radioactive iodine–refractory DTC who had progressive disease following treatment with anti-VEGFR agents.2 Cabozantinib was found to significantly reduce the risk of disease progression or death compared with placebo within the intent-to-treat population (P <.0001). After a follow up of 10.1 months, investigators reported a median progression-free survival of 11.0 months in the cabozantinib arm (n = 170) compared with 1.9 months in the placebo arm (n = 88; HR, 0.22; 95% CI, 0.15-0.31).

“Before today, patients with radioactive iodine–refractory differentiated thyroid cancer who have progressed following prior VEGFR-targeted therapy were facing aggressive disease and no standard treatment option,” Marcia S. Brose, MD, PhD, chief of Cancer Center Operation at Sidney Kimmel Cancer Center at Jefferson Torresdale Hospital; co-director, community-based clinical Trials, Sidney Kimmel Cancer Center at Thomas Jefferson University; and principal investigator of COSMIC-311, said in a press release. “In the COSMIC-311 pivotal phase 3 trial, Cabometyx extended the time patients live without progression of their cancer. The FDA approval of Cabometyx is an important advancement for these patients who are badly in need of new treatment options.”

The most common adverse effects (AEs) reported in 25% of patients were diarrhea, palmar-plantar erythrodysesthesia, fatigue, hypertension, and stomatitis. Additionally, common grade 3/4 AEs included palmar-plantar erythrodysesthesia, hypertension, fatigue, diarrhea, and stomatitis. A total of 34% of patients who were treated with cabozantinib experienced serious AEs, the most common of which were diarrhea, pleural effusion, pulmonary embolism, and dyspnea. Fatal AEs such as arterial hemorrhage (0.8%) and pulmonary embolism (0.8%) affected 1.6% of those in the cabozantinib arm. Moreover, 56% of those in the experimental arm required an initial dose reduction and 22% required a secondary dose reduction. Five percent of patients experienced AEs leading to discontinuation.

“Patients with differentiated thyroid cancer who have progressed following prior therapy and are radioactive iodine-refractory often face a poor prognosis and have limited treatment options,” Gary Bloom, executive director of ThyCa: Thyroid Cancer Survivors’ Association, said in a statement. “We are excited about the latest approval of Cabometyx, which will offer hope for patients with this type of thyroid cancer.”

Cabozantinib previously received a priority review designation from the FDA on August 5, 2021 within the same patient population based on findings from COSMIC-311.3


  1. Exelixis Announces U.S. FDA Approval of CABOMETYX® (cabozantinib) for Patients with Previously Treated Radioactive Iodine-Refractory Differentiated Thyroid Cancer. News release. Exelixis. September 17, 2021. Accessed September 17, 2021. https://bwnews.pr/2VNSZJw
  2. Brose MS, Robinson B, Sherman SI, et al. Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2021;22(8):1126-1138. doi:10.1016/S1470-2045(21)00332-6
  3. Exelixis announces U.S. FDA accepts for priority review the supplemental new drug application for Cabometyx (cabozantinib) for patients with previously treated radioactive iodine-refractory differentiated thyroid cancer. News release. August 5, 2021. Accessed September 17, 2021. https://bwnews.pr/3AieHUP

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