Cabometyx Approved for Advanced Neuroendocrine Tumors

The Food and Drug Administration (FDA) has approved Cabometyx^® (cabozantinib) for the treatment of adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET) and well-differentiated extra-pancreatic neuroendocrine tumors (epNET).

The approval for use in advanced neuroendocrine tumors is supported by data from the phase 3 CABINET trial (ClinicalTrials.gov Identifier: NCT03375320). The double-blind, placebo-controlled study included 298 patients (pNET cohort: n=99; epNET cohort: n=199) who were randomly assigned 2:1 to receive cabozantinib 60mg orally once daily or placebo until disease progression or unacceptable toxicity. Patients randomized to placebo could crossover to cabozantinib upon confirmation of progressive disease. The primary endpoint was progression free survival (PFS) assessed by a blinded independent radiology review committee per RECIST 1.1. 

Results from the pNET cohort showed cabozantinib statistically significantly improved PFS compared with placebo (median PFS: 13.8 months [95% CI, 8.9-17.0] vs 3.3 months [95% CI, 2.8-5.7]; hazard ratio [HR], 0.22 [95% CI, 0.12-0.41]; P <.0001). Overall response rate (ORR) was 18% (95% CI, 10-30) with cabozantinib and 0% (95% CI, 0-11) with placebo. Duration of response (DOR) was 11.4 months (95% CI, 6.1, not evaluable) in the cabozantinib group and not evaluable in the placebo group. 

Overall survival (OS) data were not mature. At the time of analysis, there were 32 deaths (48%) in the cabozantinib arm and 17 deaths (52%) in the placebo arm (HR, 1.01 [95% CI, 0.55-1.83]). Fifty-two percent of placebo patients had crossed over to open-label cabozantinib.

Similarly, in the epNET cohort, a statistically significant improvement in PFS was observed with cabozantinib compared with placebo (median PFS: 8.5 months [95% CI, 6.8-12.5] vs 4.2 months [95% CI, 3.0-5.7]; HR, 0.40 [95% CI, 0.26-0.61]; P <.0001). The ORR was 5% (95% CI, 2.2-11) with cabozantinib and 0% (95% CI, 0-5) with placebo. The DOR was 8.3 months (95% CI, 4.5, not evaluable) in the cabozantinib group and not evaluable in the placebo group.

Regarding OS, data were not mature at the time of analysis. There were 83 (63%) deaths in the cabozantinib arm and 40 (60%) deaths in the placebo arm (HR, 1.05 [95% CI, 0.71-1.54]). Thirty-seven percent of the placebo arm patients had crossed over to open-label cabozantinib.

The safety profile of cabozantinib was observed to be consistent with findings reported in prior clinical trials. No new safety signals were identified in the CABINET trial.

“It was encouraging to see that cabozantinib resulted in significant delays in disease progression in the CABINET trial—regardless of primary tumor site and grade,” said Jennifer Chan, MD, MPH, study chair for the CABINET trial, Clinical Director of the Gastrointestinal Cancer Center and Director of the Program in Carcinoid and Neuroendocrine Tumors at Dana-Farber Cancer Institute. “This FDA approval marks a meaningful advancement, which may establish an important new treatment option for patients, without limitations based on somatostatin receptor expression and functional status.”

Cabometyx is also indicated for the treatment of renal cell carcinoma, hepatocellular carcinoma, and differentiated thyroid cancer.

This article originally appeared on MPR