Efficacy and Safety Outcomes Support Approval of Cabozantinib in NETs

Jennifer Chan, MD, MPH, clinical director at the Gastrointestinal Cancer Center and director for the Program in Carcinoid and Neuroendocrine Tumors at Dana-Farber Cancer Institute and associate professor of medicine at Harvard Medical School, discussed the findings from the phase 3 CABINET trial (NCT03375320) leading to the FDA approval of cabozantinib (Cabometyx) in patients with neuroendocrine tumors.

The study enrolled 2 cohorts of patients with pancreatic neuroendocrine tumors (pNETs) and extrapancreatic neuroendocrine tumors (epNETs) to receive either cabozantinib or placebo. The primary end point was progression-free survival (PFS). According to Chan, the study was stopped in August 2023 due to an interim analysis showing superiority for cabozantinib. In the epNET cohort, there was an HR favoring cabozantinib of 0.38 (95% CI, 0.25-0.59; P < 0.001) whereas in the pNET cohort, there was an HR of 0.23 (95% CI, 0.12-0.42; P < 0.001).

Chan says there were no unexpected safety signals based on the known safety profile of cabozantinib, with common adverse events (AEs) such as hypertension, diarrhea, and fatigue being reported. Serious AEs were similar in nature with the addition of a low rate of thromboembolic events in the pNET cohort.

TRANSCRIPTION

0:10 | The primary end point for this study, so the primary outcome was PFS, and the trial was stopped early in August 2023 based on an interim analysis that showed superiority for cabozantinib vs placebo. So, the main final outcome was that there was in both groups of patients, in both the epNET patients and the pNET patients, an improvement in PFS,. Specifically in the cohort of patients that had pNETs, there was a 77% reduction in the risk of disease progression or death, and in the epNET cohort of patients, there was a 62% reduction in disease PFS.

0:58 | There were no unexpected AEs. What we observed for safety was very consistent with what has been observed for cabozantinib in other disease settings. Some of the common AEs that we observed in patients who were receiving cabozantinib have included, for instance, hypertension, diarrhea, [and] fatigue. In some of the higher-grade adverse events, the more serious AEs again [were] overlapping where it was also hypertension, diarrhea, fatigue, and in patients with pNETs, there were thromboembolic events that we observed, but these were not new safety signals.