Exelixis announced positive results from a subgroup analysis of the Phase 3 CABINET study, demonstrating that cabozantinib significantly improved progression-free survival (PFS) in patients with advanced gastrointestinal neuroendocrine tumors (GI NETs). The data, presented at the American Society of Clinical Oncology 2025 Gastrointestinal Cancers Symposium (ASCO GI 2025), highlight the potential of cabozantinib to become a new standard of care for this patient population. The study's findings could offer a much-needed option for individuals with GI NETs, where treatment options are currently limited.
Improved Progression-Free Survival
The subgroup analysis included 116 patients with GI NETs, a subset of the extra-pancreatic neuroendocrine tumor (epNET) cohort in the CABINET trial. Results showed that cabozantinib was associated with a statistically significant improvement in PFS compared to placebo (hazard ratio: 0.50; 95% confidence interval: 0.28-0.88; one-sided stratified log-rank P=0.007). The median PFS was 8.5 months in the cabozantinib arm compared to 5.6 months in the placebo arm.
"This subgroup analysis from the CABINET study showed that cabozantinib improved progression-free survival for patients with tumors arising in the GI tract and provides a more detailed picture of how patients with the most common form of this cancer may benefit from this treatment," said Jonathan Strosberg, M.D., President Emeritus, North American Neuroendocrine Tumor Society and Chair, GI Research Program, Moffitt Cancer Center and Research Institute.
Broad Clinical Benefit
Cabozantinib demonstrated potential benefits across various clinical factors, including tumor grade, functional status, concurrent somatostatin analog use, and prior therapy with Lu-177 dotatate or everolimus. Notably, one patient in the cabozantinib arm achieved a partial response, while none were observed in the placebo arm. Additionally, 48 patients on cabozantinib achieved stable disease compared to 30 on placebo.
Safety Profile
The safety profile of cabozantinib in patients with GI NETs was consistent with its known safety profile. The most frequent grade 3/4 adverse events included hypertension (19% in the cabozantinib arm vs. 4% in the placebo arm), diarrhea (13% vs. 4%), and fatigue (10% vs. 4%). Three grade 5 events occurred in the cabozantinib arm, potentially related to the drug, including one cardiac arrest and two unspecified events.
Regulatory Pathway
Exelixis' supplemental New Drug Application (sNDA) for cabozantinib in previously treated advanced neuroendocrine tumors is currently under review by the U.S. FDA, with a Prescription Drug User Fee Act (PDUFA) target action date of April 3, 2025. The FDA has scheduled an Oncologic Drugs Advisory Committee (ODAC) meeting in March 2025 to discuss the application.
"These new data add to the robust results from the CABINET trial that demonstrate the benefits of cabozantinib across a wide range of patients with neuroendocrine tumors and further underscore the potential of cabozantinib to become a much-needed new option for those with GI NET, which accounts for the majority of real-world patients with this tumor type," said Amy Peterson, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis.
