Cabozantinib demonstrated significant improvement in progression-free survival in patients with radioiodine-refractory differentiated thyroid cancer who have progressed after up to 2 prior vascular endothelial growth factor receptor-targeted therapies compared with placebo, meeting the primary end point of the pivotal phase 3 COSMIC-311 clinical trial.
Cabozantinib (Cabometyx) demonstrated significant improvement in progression-free survival (PFS) in patients with radioiodine-refractory differentiated thyroid cancer (DTC) who have progressed after up to 2 prior vascular endothelial growth factor receptor (VEGFR)-targeted therapies compared with placebo, meeting the primary end point of the pivotal phase 3 COSMIC-311 clinical trial (NCT03690388).
Interim analysis results showed that treatment with cabozantinib specifically led to a 78% reduction in the risk of disease progression or death with a hazard ratio of 0.22 (96% CI, 0.13-0.36; P <.0001). It was also shown during the analysis that cabozantinib had a safety profile consistent with previous observations of the drug. These results led the independent data monitoring committee to recommend stopping trial enrollment and unblinding the study sites and patients. The developer of cabozantinib, Exelixis, Inc, also plans on a regulatory filing with the FDA regarding the data for cabozantinib soon.
“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,” said 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, in a statement. “These encouraging results from COSMIC-311 suggest cabozantinib has the potential to become an important new option for these patients. We look forward to sharing the detailed data from the trial at an upcoming medical meeting.”
COSMIC-311 is a multicenter, randomized, double-blind, placebo-controlled phase 3 pivotal trial. The target enrollment for the study is 300 patients who will be treated at 150 sites worldwide. Patients in the are randomized 2:1 to receive either cabozantinib at 60 mg or matching placebo once daily.
Eligibility for enrollment requires patients to have a histologically or cytologically confirmed diagnosis of DTC, Measurable disease per RECIST version 1.1 criteria, be previously treated or considered ineligible for iodine- 131 therapy, be previously treated with at least one of the following VEGFR-targeting tyrosine kinase inhibitor (TKI) agents for DTC and have an ECOG performance status of 0 or 1.
The trial excluded patients who were previously treated with cabozantinib, a selective small-molecule BRAF kinase inhibitor, or more than 2 VEGFR-targeting TKIs. Patients were also ineligible to enroll in COSMIC-311 if they were treated with a small molecule kinase inhibitor within 2 weeks of starting the trial, an anticancer antibody anticancer antibody with 4 weeks, and radiotherapy within 4 weeks of randomization. Individuals with brain metastases or cranial epidural disease were also excluded from the trial unless the condition was adequately treated.
COSMIC-311 is ongoing and detailed results from the study are expected to be submitted for presentation at a future medical meeting.
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. Exelixis, Inc. December 21, 2020. Accessed December 22, 2020. https://bit.ly/38uwBqP