Final results from the Phase III CABINET trial reveal that cabozantinib significantly improves progression-free survival (PFS) in patients with advanced neuroendocrine tumors (NETs). The study, which included cohorts with pancreatic NETs (pNET) and extra-pancreatic NETs (epNET), demonstrated a statistically significant and clinically meaningful improvement in PFS compared to placebo. These findings, presented at the European Society of Medical Oncology (ESMO) Congress 2024 and published in the New England Journal of Medicine, suggest that cabozantinib could become a new standard of care for patients with previously treated advanced NETs.
Dramatic Improvements in Progression-Free Survival
The CABINET trial met its primary objective in both cohorts. In the pNET cohort, the median PFS was 13.8 months for cabozantinib compared to 4.4 months for placebo (HR 0.23, 95% CI: 0.12-0.42, p<0.0001). Similarly, in the epNET cohort, the median PFS was 8.4 months for cabozantinib versus 3.9 months for placebo (HR 0.38, 95% CI: 0.25-0.59, p<0.0001).
"Given that there is no standard treatment for patients with progressive disease, these results showing notable improvements in progression-free survival are highly encouraging for patients and their physicians," said Dr. Jennifer Chan, Clinical Director of the Gastrointestinal Cancer Center and Director of the Program in Carcinoid and Neuroendocrine Tumors at Dana-Farber Cancer Institute.
Consistent Benefits Across Subgroups
Additional analyses indicated that cabozantinib provided benefits across all clinical subgroups examined, including primary tumor site, grade, and prior systemic anticancer therapy. The objective response rate (ORR) in the pNET cohort was 19% with cabozantinib compared to 0% with placebo. In the epNET cohort, the ORR was 5% with cabozantinib compared to 0% with placebo.
Safety Profile
The safety profile of cabozantinib in the CABINET trial was consistent with previous studies. Common side effects included hypertension, fatigue, and diarrhea, with no new safety signals identified.
Regulatory Implications
Exelixis submitted a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) for cabozantinib based on these results. The FDA accepted the sNDA in August and assigned a Prescription Drug User Fee Act (PDUFA) target action date of April 3, 2025.
Study Design
The CABINET trial is a multicenter, randomized, double-blinded, placebo-controlled Phase III study that enrolled 298 patients with advanced NETs in two cohorts (pNET, n=95; epNET, n=203). Patients had experienced disease progression after at least one FDA-approved line of prior therapy other than somatostatin analogs. The primary endpoint was PFS in each cohort. Patients on placebo were allowed to cross over to open-label cabozantinib upon disease progression.
