The Food and Drug Administration has approved Cabometyx® (cabozantinib) for the treatment of patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer that has progressed following prior vascular endothelial growth factor receptor (VEGFR)-targeted therapy and who are radioactive iodine-refractory or ineligible.
The approval was based on data from the phase 3 COSMIC-311 study (ClinicalTrials.gov Identifier: NCT03690388), which compared the efficacy and safety of Cabometyx, a kinase inhibitor, to placebo in patients with radioiodine-refractory differentiated thyroid cancer who had progressed after up to 2 prior vascular endothelial growth factor receptor-targeted therapies. Patients were randomly assigned 2:1 to receive either Cabometyx 60mg orally once daily or placebo.
The coprimary endpoints were progression-free survival (PFS) in the intent-to-treat population, and overall response rate in the first 100 randomized patients, as assessed by blinded independent radiology review committee per RECIST 1.1.
At a planned interim analysis, results showed that treatment with Cabometyx demonstrated a statistically significant improvement in PFS. At a median follow-up of 6.2 months, the median PFS was not reached (96% CI, 5.7 months-not estimable) in the Cabometyx arm and was 1.9 months (96% CI, 1.8-3.6) for placebo (hazard ratio, 0.22 (96% CI, 0.14–0.35; P <.0001). Though not statistically significant, the ORR was 15% (95% CI, 7-26) for Cabometyx vs 0% (95% CI, 0.0-11) for placebo (P =.0281).
At a follow-up analysis with a median follow-up of 10.1 months, the median PFS was 11.0 months (96% CI, 7.4-13.8) in the Cabometyx arm and 1.9 months (96% CI, 1.9-3.7) in the placebo arm (hazard ratio, 0.22; 96% CI, 0.15–0.31). The ORR was 18% (95% CI, 10-29) for Cabometyx vs 0% (95% CI, 0.0-11) for placebo.
The updated findings will be presented at the 2021 European Society of Medical Oncology (ESMO) Congress this month.
Cabometyx is approved for the treatment of advanced renal cell carcinoma as a single agent, or in combination with nivolumab as a first-line treatment of advanced renal cell carcinoma and for hepatocellular carcinoma in patients who have been previously treated with sorafenib.
The product is available as 20mg, 40mg, and 60mg tablets in 30-count bottles.
- Exelixis announces US FDA approval of Cabometyx® (cabozantinib) for patients with previously treated radioactive iodine-refractory differentiated thyroid cancer. News release. Exelixis, Inc. Accessed September 20, 2021. https://www.businesswire.com/news/home/20210917005517/en/Exelixis-Announces-U.S.-FDA-Approval-of-CABOMETYX%C2%AE-cabozantinib-for-Patients-with-Previously-Treated-Radioactive-Iodine-Refractory-Differentiated-Thyroid-Cancer.
- Cabometyx. Package insert. Exelixis, Inc.; 2021. Accessed September 20, 2021. https://www.cabometyx.com/downloads/CABOMETYXUSPI.pdf.