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TOPLINE:

Cabozantinib improves progression-free survival (PFS) in patients with advanced extrapancreatic neuroendocrine tumors and pancreatic neuroendocrine tumors compared with placebo.

METHODOLOGY:

• Cabozantinib, an oral small-molecule inhibitor targeting multiple tyrosine kinases, including vascular endothelial growth factor receptors MET, AXL, and RET, showed promising activity in a phase 2 trial.
• The new multicenter, phase 3 trial enrolled 298 patients with advanced neuroendocrine tumors in two independent cohorts — 203 with extrapancreatic tumors and 95 with pancreatic tumors — who had received prior peptide receptor radionuclide therapy or targeted therapy.
• Participants were randomly assigned in a 2:1 ratio to receive either 60 mg/d cabozantinib or placebo, with stratification based on concurrent somatostatin analogue use and primary tumor site.
• Primary endpoint was PFS assessed by blinded independent central review, with objective response, overall survival, and safety as key secondary endpoints.
• Analysis included patients with well-differentiated or moderately differentiated neuroendocrine tumors of World Health Organization grades 1-3, requiring disease progression within 12 months before enrollment.

TAKEAWAY:

• Cabozantinib demonstrated superior efficacy with a median PFS of 8.4 months vs 3.9 months with placebo in extrapancreatic neuroendocrine tumors (stratified hazard ratio [HR], 0.38; 95% CI, 0.25-0.59; P < .001).
• Patients with pancreatic neuroendocrine tumors showed improved median PFS of 13.8 months with cabozantinib compared with 4.4 months with placebo (HR, 0.23; 95% CI, 0.12-0.42; P < .001).
• Objective response rates were higher with cabozantinib at 5% and 19% for extrapancreatic and pancreatic neuroendocrine tumors, respectively, compared with 0% with placebo.
• Treatment-related adverse events of grades ≥ 3 included hypertension, fatigue, diarrhea, and thromboembolic events, affecting 62%-65% of cabozantinib-treated patients vs 23%-27% of placebo recipients.

IN PRACTICE:

“Cabozantinib, compared with placebo, resulted in longer progression-free survival in patients with extrapancreatic neuroendocrine tumors or pancreatic neuroendocrine tumors that had progressed after previous therapy with Lu-177 [Lutetium-177] dotatate or targeted agents, including everolimus or sunitinib. Adverse events, which were managed with dose reduction in a majority of the patients, were consistent with the known safety profile of cabozantinib,” wrote the authors of the study.

SOURCE:

The study was led by Jennifer A. Chan, MD, MPH, of the Dana-Farber Cancer Institute in Boston. It was published online on September 16 in The New England Journal of Medicine.

LIMITATIONS:

According to the authors, early termination of the trial based on interim analysis results could potentially lead to overestimation of the treatment effect, though the analyses represent relatively mature PFS data. The use of placebo as control rather than an active comparator was noted as another limitation, though justified by the lack of established efficacy for treatments after progression on Lu-177 dotatate or targeted agents.

DISCLOSURES:

The study was supported by grants from the National Cancer Institute of the National Institutes of Health and Exelixis.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.