Cabozantinib may prolong progression-free survival in patients with previously treated, progressive advanced extrapancreatic or pancreatic neuroendocrine tumors, according to a recent study.

In the phase III trial (ClinicalTrials.gov identifier NCT03375320), published in The New England Journal of Medicine, researchers evaluated 298 patients in two independent cohorts, showing a substantial reduction in disease progression risk. In the extrapancreatic cohort (n = 203), median progression-free survival (PFS) was 8.4 months with cabozantinib vs 3.9 months with placebo (hazard ratio [HR] = 0.38, 95% confidence interval [CI] = 0.25–0.59, P < .001). In the pancreatic cohort (n = 95), cabozantinib achieved a median PFS of 13.8 months compared with 4.4 months with placebo (HR = 0.23, 95% CI = 0.12–0.42, P < .001).

Confirmed objective response rates (partial response) were 5% and 19% in the extrapancreatic and pancreatic cohorts, respectively, while stable disease was the most common response (65% and 61%). None of the patients in the placebo group showed a partial response.

Grade 3 or higher treatment-related adverse events occurred in 62% to 65% of the patients who received cabozantinib vs 23% to 27% of those who received placebo. Common adverse events included hypertension (21% to 22%), fatigue (11% to 13%), and diarrhea (11%). Dose reductions were required in 66% and 68% of cabozantinib-treated patients in the extrapancreatic and pancreatic cohorts, respectively, while treatment discontinuation as a result of adverse events occurred in 31% and 20%.

"Cabozantinib was associated with a 62% lower risk of disease progression or death, on average," said lead study author Jennifer A. Chan, MD, MPH, of the Dana-Farber Cancer Institute, and her colleagues.

The findings supported cabozantinib as a potential treatment option for progressive neuroendocrine tumors following peptide receptor radionuclide therapy or targeted therapy. The researchers emphasized the importance of individualized treatment selection based on patient and tumor characteristics.

The trial, funded by the National Cancer Institute and other organizations, was terminated early as a result of significant efficacy signals. Further research is needed to explore sequencing strategies and overall survival impact.

Full disclosures are detailed in the study.