FDA Approves Cabozantinib for RAI-Refractory Locally Advanced or Metastatic DTC

The FDA has approved cabozantinib (Cabometyx) for the treatment of patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior vascular endothelial growth factor receptor (VEGFR)-targeted therapy and who are radioactive iodine-refractory or ineligible, according to a press release by Exelixis Inc.¹

In addition to DTC, cabozantinib also holds several indications in renal cell carcinoma. The agent has also been approved in the European Union.

The approval is based on the results of the phase 3 COSMIC-311 study (NCT03690388). The randomized, parallel assignment study has an actual enrollment of 258 participants and an estimated completion date of December 2022. Primary end points of the study include progression-free survival (PFS) and objective response rate (ORR).²

Patients were randomized 2:1 to receive either 60mg of cabozantinib once daily or a matching placebo.

A planned interim analysis found that at a median follow-up of 10.1 months, the median PFS for the cabozantinib group was 11 months and 1.9 months in the placebo group (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,” said Marcia S. Brose, MD, PhD, chief of Cancer Center Operation at Sidney Kimmel Cancer Center at Jefferson Torresdale Hospital, co-director of Community Based Clinical Trials, Sidney Kimmel Cancer Center at Thomas Jefferson University, and principal investigator of COSMIC-311, 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.”

Common adverse events (AEs) were diarrhea, palmar-plantar erythrodysesthesia, fatigue, hypertension and stomatitis. Grade 3/4 AEs that occurred in at least 5% of patients in the cabozantinib arm were palmar-plantar erythrodysesthesia, hypertension, fatigue, diarrhea and stomatitis. Dose reductions were required in 56% of patients in the cabozantinib arm and 22% of patients required a second dose reduction. AEs led to discontinuation in 5% of patients.

“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, in a press release. “We are excited about the latest approval of Cabometyx, which will offer hope for patients with this type of thyroid cancer.”

_REFERENCES:

_{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 20, 2021. https://bit.ly/2XvRyjF.}

_{2.A study of cabozantinib compared with placebo in subjects with radioiodine-refractory differentiated thyroid cancer who have progressed after prior vascular endothelial growth factor receptor (VEGFR) -targeted therapy. Clinicaltrials.gov. https://bit.ly/3kqvdwN.}