Improved Survival Observed in CABINET Trial of Pancreatic NETs

Jason S. Starr, DO, assistant professor of medicine and a hematologist/oncologist in the Department of Internal Medicine at Mayo Clinic, discusses the CABINET trial (NCT03375320) of cabozantinib (Cabometyx) in pancreatic neuroendocrine tumors (NETs).

Cabozantinib, a tyrosine kinase inhibitor (TKI), was recently approved for patients with previously treated pancreatic NETs. Starr notes there was a long period of time where TKIs were tested in this setting and did not show efficacy until the phase 2 findings for cabozantinib.

The phase 3 CABINET trial demonstrated the efficacy of cabozantinib in advanced pancreatic NETs. The data showed a significant improvement in progression-free survival (PFS), at a median of 13.8 months in the cabozantinib arm vs 4.4 months in the placebo arm (stratified HR, 0.23; 95% CI, 0.12 to 0.42; P < .001). This compared favorably to the historical benchmark of 11.5 months set by sunitinib (Sutent), another TKI approved in this setting. Cabozantinib also had an objective response rate of 19%, more than double the rate historically associated with sunitinib, Starr says.

TRANSCRIPTION

0:10 | Cabozantinib is the new kid on the block as far as treatment options are concerned for NETS, and we have had experience with TKIs such as cabozantinib for some time. In 2011, sunitinib is the tried-and-true [treatment], if you will, and was approved by the FDA for pancreatic NETs. So there's been a large gap in time in which a lot of different TKIs, which are oral therapies that we give, have come and went. We've done studies, phase 2 studies, that have looked positive, but they haven't come to fruition for patient use.

0:56 | Then for cabozantinib, the phase 2 data were really exciting, and that is when the phase 3 [trial] was launched. It was launched as the CABINET study. It was run as a cooperative group study, which was primarily within the [Alliance for Clinical Trials in Oncology]. Dr Jennifer Chan, [MD, MPH,] was the principal investigator, and essentially, they looked at about 300 patients and they divided out the groups into patients with pancreatic NETs and extrapancreatic NETs. Patients were [randomly assigned] to the cabozantinib vs placebo in each one of those groups. The data were exciting, and for pancreatic NETs, we saw that the [median] PFS was almost 15 months, which compared favorably—got to be careful with cross-trial comparison—to sunitinib, which was about 11 and a half months, so favorable. The response rate was about 20% or 19%, which compares with around 9% with historically sunitinib.