CABINET: Updated PFS, Subgroup Analyses of Cabozantinib Versus Placebo for Advanced NET

Cabozantinib continues to demonstrate “significant” improvement in progression-free survival (PFS) by blinded independent central review (BICR) in extra-pancreatic neuroendocrine tumors (epNET) or pancreatic NET (pNET), according to the latest update from the phase 3 CABINET trial/Alliance A021602. Data are presented at the European Society for Medical Oncology Congress 2024.

Previous research has shown that VEGF pathway inhibitors are active against NETs. In CABINET/A021602, cabozantinib, a multi-kinase inhibitor targeting VEGFR, c-MET, AXL, and RET, was compared to the placebo that included previously treated patients with advanced NETs. The study was stopped early and unblinded because interim results showed improvement in PFS by local radiology assessment.

In the study, Dr. Jennifer Chan and colleagues included patients with locally advanced or metastatic epNET or pNET and randomized them (2:1) to receive cabozantinib (60 mg daily) or placebo. Patients were deemed eligible based on RECIST within 12 months prior to registration and at least one line of previous therapy.

As of the data cut-off of August 24, 2023, 203 patients with epNET and 95 patients with pNET were randomized in CABINET/A021602. The primary tumor sites for patients with epNET included gastrointestinal tract (57%), lung (19%), and unknown (12%).

In both cohorts, Dr. Chan and colleagues found that cabozantinib significantly improved PFS by BICR and resulted in higher confirmed objective response rate. Similarly, across clinical subgroups like primary tumor site and prior anticancer therapy, PFS was higher in patients receiving cabozantinib.

While grade 3 or higher treatment-related adverse events—including hypertension, fatigue, and diarrhea—were reportedly higher in the cabozantinib arm, no new safety signals were observed.

These updated PFS results and subgroup data led researchers to conclude that “Cabozantinib may be a new treatment option for patients with previously treated, advanced NET.”