On September 17, 2021, the FDA accelerated the approval of a new indication for cabozantinib (Cabometyx; Exelixis) for the treatment of patients aged ≥12 years with locally advanced or metastatic differentiated thyroid cancer that has progressed after VEGFR-targeted therapy and who are ineligible for, or whose disease is refractory to, radioactive iodine. The FDA granted cabozantinib breakthrough therapy and orphan drug designations for this indication.
“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, Jefferson Torresdale Hospital, 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.”
“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,” said Gary Bloom, Executive Director of ThyCa: Thyroid Cancer Survivors’ Association. “We are excited about the latest approval of Cabometyx, which will offer hope for patients with this type of thyroid cancer.”
Cabozantinib was previously approved for several indications. This new approval was based on the COSMIC-311 study, a randomized, double-blind, placebo-controlled, multicenter clinical trial of patients with locally advanced or metastatic differentiated thyroid cancer that had progressed after VEGFR-targeted therapy and who were ineligible for or refractory to radioactive iodine.
Patients were randomized in a 2:1 ratio to cabozantinib 60 mg orally once daily or to placebo and best supportive care until disease progression or intolerable adverse events. The primary efficacy measures were progression-free survival (PFS) in the intent-to-treat population and overall response rate (ORR) in the first 100 randomized patients.
Cabozantinib significantly reduced the risk for disease progression or death versus placebo (P <.0001). The median PFS was 11 months with cabozantinib versus 1.9 months with placebo. The ORR was 18% in the cabozantinib arm and 0% in the placebo arm.
The most common (≥25%) adverse events in the study were diarrhea, palmar-plantar erythrodysesthesia, fatigue, hypertension, and stomatitis. A warning was added to the prescribing information about the risk for hypocalcemia.