U.S. Food and Drug Administration approves cabozantinib-Cabometyx for pNET and epNET

Cabozantinib (Cabometyx, cabozantinib) developed byExelixis has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult and pediatric patients 12 years of age and older who have previously received treatment for unresectable, locally advanced, or metastatic well-differentiated pancreatic neuroendocrine tumors (pNET) and well-differentiated extrapancreatic neuroendocrine tumors (epNET).

The efficacy of cabozantinib in patients with neuroendocrine tumors (NET) was evaluated in a clinical trial called CABINET (clinical trial registration number: NCT 03375320). This is a multicenter, double-blind, placebo-controlled, randomized trial involving two main cohorts, pNET and epNET, with a total of 298 patients participating. All patients were patients with unresectable, locally advanced or metastatic pNET who had disease progression on the basis of previous treatments.

In both cohorts, the primary efficacy outcome measure was progression-free survival (PFS), as assessed by a blinded radiologic review committee according to RECIST 1.1. In addition, other efficacy outcome measures include overall response rate (ORR) and overall survival rate (OS).

In the pNET cohort, a total of 99 patients were randomly assigned in a 2:1 ratio to receive 60 mg of oral cabozantinib or placebo once daily until disease progression or unacceptable toxicity. Among patients who received cabozantinib, median PFS was 13.8 months (95% confidence interval [CI], 8.9-17.0 months) compared with only 3.3 months (95% CI, 2.8-5.7 months) in the placebo group. The hazard ratio (HR) was 0.22 (95% CI, 0.12-0.41; P<0.0001), indicating that cabozantinib significantly prolonged progression-free survival. The ORRs of the two groups were 18% (95% CI, 10%-30%) and 0% (95% CI, 0-11%) respectively, showing that cabozantinib has a significant efficacy compared with placebo. However, data on OS are immature, with 32 deaths in the cabozantinib group (48% of patients enrolled) and 17 deaths in the placebo group (52% of patients enrolled), with a HR of 1.01 (95% CI, 0.55-1.83). Of note, 52% of patients in the placebo group switched to open-label cabozantinib, which may have had an impact on OS estimates.

ForIn the epNET cohort, 199 patients were also randomly assigned to the cabozantinib group or the placebo group in a ratio of 2:1 and received the same treatment regimen until disease progression or unacceptable toxicity. The median PFS of the cabozantinib group was 8.5 months (95% CI, 6.8-12.5 months), while the median PFS of the placebo group was 4.2 months (95% CI, 3.0-5.7 months), and the HR was 0.40 (95% CI, 0.26-0.61; P<0.0001), which also showed that cabozantinib has a significant advantage in prolonging progression-free survival. The ORRs of the two groups were 5% (95% CI, 2.2%-11%) and 0% (95% CI, 0-5%) respectively. Data on OS remain immature, with 83 deaths (63% of enrolled patients) in the cabozantinib group and 40 (60% of enrolled patients) in the placebo group, for a HR of 1.05 (95% CI, 0.71-1.54). Similarly, 37% of patients in the placebo group ultimately switched to open-label cabozantinib, which may also affect the assessment of OS.

References:https://www.gastroendonews.com/FDA-Update-and-Product-News/Article/03-25/FDA-Approves-Cabometyx-for-pNET-and-epNET/76617