The FDA granted approval for cabozantinib (Cabometyx, Exelixis) for adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumor (pNET) and well-differentiated extra-pancreatic neuroendocrine tumor (epNET).
Efficacy of cabozantinib for patients with NET was evaluated in CABINET (ClinicalTrials.gov. Identifier: NCT03375320), a multicenter, double-blind, placebo-controlled trial with two separate randomized cohorts (pNET and epNET) of 298 patients with unresectable, locally advanced or metastatic pNET that had progressed on prior therapy.
In both cohorts, the major efficacy outcome measure was progression-free survival (PFS), assessed by a blinded independent radiology review committee per RECIST 1.1. Additional efficacy outcome measures included overall response rate (ORR) and overall survival (OS).
The pNET cohort included 99 patients randomized (2:1) to receive cabozantinib 60 mg orally once daily or placebo until disease progression or unacceptable toxicity. The median PFS was 13.8 months (95% 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, 0.12-0.41; P<0.0001). The ORR was 18% (95% CI, 10%-30%) and 0 (95% CI, 0-11%) in the respective arms. Data on OS were not mature, with 32 (48% of patients enrolled) deaths in the cabozantinib arm and 17 (52% of patients enrolled) deaths in the placebo arm (HR, 1.01; 95% CI, 0.55-1.83). In the placebo arm, 52% of patients crossed over to open-label cabozantinib, which may change the evaluation of OS.
The epNET cohort included 199 patients randomized (2:1) to receive the above regimen of cabozantinib or placebo until disease progression or unacceptable toxicity. The median PFS 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<0.0001). The ORR was 5% (95% CI,2.2%-11%) and 0 (95% CI, 0-5%) in the respective arms. Data on OS were not mature, with 83 (63% of patients enrolled) deaths in the cabozantinib arm and 40 (60% of patients enrolled) in the placebo arm (HR, 1.05; 95% CI, 0.71-1.54). In the placebo arm, 37% crossed over to open-label cabozantinib, which may alter the evaluation of OS.
The safety profile of cabozantinib was consistent with the approved product label.
The full prescribing information for cabozantinib will be posted at Drugs@FDA.
—GEN Staff
Based on a press release from the FDA.
Originally published by our sister publication Clinical Oncology News