The FDA recently approved cabozantinib (Cometriq), for the treatment of patients with progressive metastatic medullary thyroid cancer. Cabozantinib is a small molecule that inhibits the activity of multiple tyrosine kinases, including RET, MET, and VEGF receptor 2.
The approval was based on the demonstration of improved progression-free survival observed in an international, multicenter, randomized (2:1), placebo-controlled trial enrolling 330 patients with metastatic medullary thyroid cancer. Patients were required to have progressive disease within 14 months prior to entry.
Patients were randomly assigned to receive cabozantinib, 140 mg (n = 219) or placebo (n = 111) orally once daily. Randomization was stratified by age and prior tyrosine kinase inhibitor use. Patients were treated until disease progression or intolerable toxicity. At the time of disease progression, crossover to cabozantinib was not permitted in patients receiving placebo. An independent radiology review committee, using the modified RECIST criteria, determined radiographic progression and tumor response.
Of 330 patients, 67% were male, the median age was 55 years, 23% were 65 years or older, 54% had a baseline ECOG performance status of 0, and 92% had undergone thyroidectomy. Twenty-five percent received two or more prior systemic therapies and 21% had been previously treated with a tyrosine kinase inhibitor.
A statistically significant progression-free survival prolongation was demonstrated in the cabozantinib arm compared to the placebo arm (HR = 0.28 [95% CI, 0.19–0.40]; P < .0001]. The estimated median progression-free survival was 11.2 and 4.0 months for the cabozantinib and placebo arms, respectively.
The overall response rate was significantly higher in the cabozantinib arm (27% vs 0%; P < .0001) and all were partial responses. The median response duration was 14.7 months (95% CI, 11.1–19.3). No statistically significant difference in overall survival was observed between the treatment arms at the planned interim analysis and in an updated survival analysis requested by FDA. ■