Dr Strosberg on Cabozantinib vs Placebo in Patients With Advanced GI NETs

"When considering similar drugs [to cabozantinib] in this space, everolimus, is strictly approved for non-hormonally functional NETs, a category that excludes many GI primaries, which are hormone-producing, functional tumors. In [the CABINET] study, however, no distinction was observed between functional and nonfunctional tumors or between small bowel/midgut and non-midgut tumors. The benefit of treatment was seen consistently across the population.”

Jonathan R. Strosberg, MD, leader, Neuroendocrine Tumor Division, leader, Department of Gastrointestinal Oncology Research Program, professor, Moffitt Cancer Center, discusses findings from a subgroup analysis of the phase 3 CABINET trial (NCT03375320) evaluating cabozantinib (Cabometyx) vs placebo in patients with advanced gastrointestinal (GI) neuroendocrine tumors (NETs) who had progressed on prior therapy.

Strosberg notes that in this subgroup analysis, investigators evaluated the safety and efficacy of cabozantinib, a TKI targeting VEGF receptors and MET, compared with placebo in 116 patients with GI NETs, representing a subset of the broader trial population. Patients were randomly assigned to receive either cabozantinib or placebo, with progression-free survival (PFS) as the primary end point and secondary analyses focusing on radiographic response and adverse effects (AEs).

Results presented at the 2025 Gastrointestinal Cancers Symposium demonstrated that cabozantinib significantly improved PFS compared with placebo, with a median PFS of 8.5 months (95% CI, 6.0-16.7) in the cabozantinib arm vs 5.6 months (95% CI, 3.9-11.0) in the placebo arm (HR, 0.50; 95% CI, 0.28-0.88; P = .007). Disease stabilization was achieved in 69% of patients in the cabozantinib arm compared with 65% of those in the placebo arm. One partial response was seen in the cabozantinib arm, and no partial responses were seen in the placebo arm.

The safety profile of cabozantinib was consistent with previously reported data, with grade 3/4 treatment-related AEs reported in 60% of patients in the cabozantinib arm vs 18% of those in the placebo arm. The most common grade 3/4 AEs associated with cabozantinib included hypertension (19%), diarrhea (13%), and fatigue (10%). No new safety signals were observed.

Strosberg emphasizes that a benefit with cabozantinib was observed across clinical subgroups, including patients with functional and nonfunctional tumors, midgut and non-midgut primaries, and those who had received prior treatment with somatostatin analogs or other systemic therapies. He highlights the need for continued exploration of cabozantinib in this population and notes that these findings support its role as a potential therapeutic option for patients with advanced GI NETs.