Cabozantinib Prolongs PFS in Patients With Previously Treated NETs

Cabozantinib improves progression-free survival (PFS) in patients with previously treated, pancreatic or extrapancreatic neuroendocrine tumors (NETs), according to research presented at the ESMO Congress 2023.

“Based on these results, cabozantinib may become a new treatment option for patients with previously treated, progressive NET,” said study presenter Jennifer Chan, MD, of Dana-Farber Cancer Institute in Boston.

These results come from the phase 3 CABINET trial (ClnicalTrials.gov identifier: NCT03375320), which included patients with advanced NETs who had received at least 1 prior line of approved therapy.

The patients were divided into an extrapancreatic NET cohort and a pancreatic NET cohort. In each cohort, patients were randomly assigned to receive either cabozantinib at 60 mg daily or placebo.

In the extrapancreatic NET cohort, there were 129 patients in the cabozantinib arm and 68 in the placebo arm. In the pancreatic NET cohort, 62 patients received cabozantinib, and 31 patients received placebo. In each cohort, baseline characteristics were considered well balanced between the treatment arms.

Dr Chan noted that accrual to the trial was stopped early based on positive PFS results seen with cabozantinib. Patients were then unblinded and allowed to cross over from the placebo arm to the cabozantinib arm. 

In the extrapancreatic NET cohort, at a median follow-up of 13.9 months, the median PFS was 8.3 months with cabozantinib and 3.2 months with placebo (hazard ratio [HR], 0.45; 95% CI, 0.30-0.66; P <.0001).

In the pancreatic NET cohort, at a median follow-up of 16.7 months, the median PFS was 11.4 months with cabozantinib and 3.0 months with placebo (HR, 0.27; 95% CI, 0.14-0.49; P <.0001).

Dr Chan noted that the overall survival (OS) data were not yet mature. However, the median OS in the extrapancreatic NET cohort was 21.9 months with cabozantinib and 22.4 months with placebo (HR, 0.90; 95% CI, 0.56-1.46; P =.34).

In the pancreatic NET cohort, the median OS was 43.5 months with cabozantinib and 31.0 months with placebo (HR, 0.77; 95% CI, 0.34-1.73; P =.26).

In the extrapancreatic NET cohort, the overall response rate (ORR) was 4% with cabozantinib and 1% with placebo. In the pancreatic NET cohort, the ORR was 18% with cabozantinib and 6% with placebo.

In both cohorts, hypertension and fatigue were the most common grade 3 or higher adverse events (AEs) among cabozantinib recipients. These AEs were consistent with the known safety profile of cabozantinib, Dr Chan said.

There were 3 deaths in the extrapancreatic NET cohort that were possibly related to cabozantinib, with 1 death due to hemorrhage and 2 due to causes not otherwise specified.

Disclosures: This study was partly supported Exelixis. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Chan J, Geyer S, Ou F-S, et al. Alliance A021602: Phase III, double-blinded study of cabozantinib versus placebo for advanced neuroendocrine tumors (NET) after progression on prior therapy (CABINET). Presented at ESMO Congress 2023. Oct. 20-24, 2023. Madrid, Spain. Abstract LBA53.

This article originally appeared on Cancer Therapy Advisor