New Frontiers in Neuroendocrine Tumors (NETs): Treatment Advances and Insights From the Phase 3 CABINET Study - Episode 5
Interpreting the Clinical Efficacy of Cabozantinib in NETs
Panelists discuss the CABINET trial’s findings that cabozantinib significantly improved progression-free survival in both pancreatic and extrapancreatic neuroendocrine tumors, highlighting its efficacy in a heavily pretreated, real-world population and noting the trial’s inclusive design, crossover protocol, and implications for broader clinical use.
The CABINET trial demonstrated that cabozantinib is an effective treatment for neuroendocrine tumors, with significant improvements in progression-free survival (PFS), particularly in pancreatic NETs. Objective response rates were modest—5% in extrapancreatic and 19% in pancreatic cohorts—but meaningful, especially considering the heavily pretreated patient population. In the pancreatic group, the PFS reached 13.8 months compared with 4.4 months with placebo, which is notable even when compared with earlier sunitinib data in less heavily treated patients. In the extrapancreatic cohort, PFS was 8.4 months vs 3.9 months with placebo, which is both statistically and clinically significant. Overall survival (OS) did not reach statistical significance in either cohort, but there was a favorable trend in the cabozantinib arms.
The trial’s design and subgroup analyses added further value. It included a wide spectrum of tumor grades (1-3), with about 10% of participants having grade 3 tumors—an underrepresented group in NET studies. The majority were grade 2, and the median number of prior therapies was 2 for extrapancreatic and 3 for pancreatic NETs, emphasizing that these were not treatment-naive patients. Additionally, around 60% of participants had previously received peptide receptor radionuclide therapy, and a high proportion had been treated with everolimus and other systemic therapies. This underscores that the trial’s population reflected real-world complexity, making the results more generalizable.
Importantly, the trial allowed crossover after interim analysis revealed underperformance in the placebo arm, leading to early unblinding. About 40% of patients crossed over to cabozantinib, with others receiving it off-label. This likely diluted OS outcomes but reinforced the ethical handling of the study. The inclusion of broad eligibility criteria—including different grades, primary tumor sites, and prior treatments—was seen as a strength. It increases the practical relevance of the findings and helps address treatment gaps, particularly in understudied subgroups like grade 3 well-differentiated NETs.
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