Cabozantinib (multi-kinase VEGFR/MET/AXL inhibitor) cuts progression risk in functional vs non-functional NET in CABINET

Cabozantinib (CABO) is an oral multi-target tyrosine kinase inhibitor (notably VEGFR2, MET, AXL) evaluated in the Phase 3 CABINET trial (NCT03375320) in progressive, previously treated advanced extrapancreatic NET (epNET) or pancreatic NET (pNET) (progressed by RECIST within 12 months; ≥1 prior systemic therapy excluding somatostatin analogs), randomized 2:1 to CABO 60 mg daily vs placebo. In this post hoc functional-status subgroup analysis (total n=298; functional NET n=74; non-functional NET n=179), CABO improved PFS vs placebo in both functional NET (sHR 0.40, 95% CI 0.20–0.82; p=0.012) and non-functional NET (sHR 0.26, 95% CI 0.17–0.41; p<0.001); concurrent SSA use was common (91% functional; 53% non-functional). Grade 3/4 AEs on CABO were typical for VEGFR TKIs—hypertension 21% (both subgroups) and fatigue 18% in non-functional NET—broadly consistent with the tradeoffs seen with other targeted options in NET (e.g., everolimus in nonfunctional GI/lung NET mPFS 11.0 vs 3.9 months vs placebo; sunitinib in pNET mPFS ~11.4 vs 5.5 months vs placebo), but note cross-trial comparisons can’t substitute for head-to-head data.