Cancer Treatment Today

Chan recently published a phase III CABINET trialof cabozantinib vs. placebo in patients with advanced neuroendocrine tumors (NET) that have progressed following prior therapy. At a median follow-up of 13.9 months, patients with extra-pancreatic NETs (epNETs) who received the TKI (n = 129) experienced a median PFS of 8.3 months vs 3.2 months with placebo (n = 68; stratified HR, 0.45; 95% CI, 0.30-0.66; P < .0001). Additionally, at a median follow-up of 16.7 months, patients with pancreatic NETs (pNETs) achieved a median PFS of 11.4 months vs 3.0 months in the cabozantinib (n = 62) and placebo (n = 31) arms, respectively (stratified HR, 0.27; 95% CI, 0.14-0.49; P < .0001).
CABINET enrolled patients with well- to moderately-differentiated, grade 1 to 3 NETs. Patients needed to have disease progression (PD) according to RECIST criteria within 12 months prior to random assignment and have PD after or intolerance of at least 1 prior FDA-approved systemic therapy, excluding somatostatin analogs. Concurrent use of somatostatin analogs was permitted if administered at a stable dose for at least 2 months.

The interim analyses and both of the cohorts showed a statistically significant and clinically meaningful difference in PFS in patients treated with cabozantinib.

There are 2 phase II studies that support these results.

Chan J, Geyer S, Ou FS, et al. Alliance A021602: Phase III, double-blinded study of cabozantinib versus placebo for advanced neuroendocrine tumors (NET) after progression on prior therapy (CABINET). Ann Oncol. 2023;34(suppl 2):S192. doi:10.1016/j.annonc.2023.10.047

J.A. Chan et al, Phase II trial of cabozantinib in patients with carcinoid and pancreatic neuroendocrine tumors (pNET). ancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
March 21, 2017

Corti F, Brizzi MP, Amoroso V, Giuffrida D, Panzuto F, Campana D, Prinzi N, Milione M, Cascella T, Spreafico C, Randon G, Oldani S, Leporati R, Scotto G, Pulice I, Stocchetti BL, Porcu L, Coppa J, Di Bartolomeo M, de Braud F, Pusceddu S. Assessing the safety and activity of cabozantinib combined with lanreotide in gastroenteropancreatic and thoracic neuroendocrine tumors: rationale and protocol of the phase II LOLA trial. BMC Cancer. 2023 Sep 26;23(1):908.