The U.S. Food and Drug Administration (FDA) recently approved the tyrosine kinase inhibitor cabozantinib (Cabometyx) for adult and pediatric patients aged 12 years and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (NETs) and well-differentiated extrapancreatic NETs.
The efficacy of cabozantinib for patients with NETs was evaluated in CABINET, a double-blind, placebo-controlled, multicenter trial. There were two separate, randomized cohorts (pancreatic NETs and extrapancreatic NETs) of 298 patients with unresectable, locally advanced, or metastatic NETs that had progressed on prior therapy.
The pancreatic NET cohort included 99 patients randomly assigned 2:1 to receive cabozantinib at 60 mg orally once daily or placebo until disease progression or unacceptable toxicity. Median progression-free survival was 13.8 months (95% confidence interval [CI] = 8.9–17.0 months) in the cabozantinib arm and 3.3 months (95% CI = 2.8–5.7 months) in the placebo arm (hazard ratio [HR] = 0.22, 95% CI = 0.12–0.4, P < .0001). The overall response rates were 18% (95% CI = 10%–30%) and 0% (95% CI = 0%–11%) in the respective arms. Overall survival data were not mature, with 32 deaths (48% of patients enrolled) in the cabozantinib arm and 17 deaths (52% of patients enrolled) in the placebo arm (HR = 1.01, 95% CI = 0.55–1.83). A total of 52% of patients in the placebo arm crossed over to receive open-label cabozantinib.
The extrapancreatic NET cohort included 199 patients randomly assigned 2:1 to receive the previously mentioned regimen of cabozantinib or placebo until disease progression or unacceptable toxicity. Median progression-free survival was 8.5 months (95% CI = 6.8–12.5 months) in the cabozantinib arm and 4.2 months (95% CI = 3.0–5.7 months) in the placebo arm (HR = 0.40, 95% CI = 0.26–0.61, P < .0001). The overall response rates were 5% (95% CI = 2.2%–11%) and 0% (95% CI = 0%–5%) in the respective arms. Overall survival data were not mature, with 83 deaths (63% of patients enrolled) in the cabozantinib arm and 40 deaths (60% of patients enrolled) in the placebo arm (HR = 1.05, 95% CI = 0.71–1.54). A total of 37% of those receiving placebo crossed over to receive open-label cabozantinib.
