Clinical Perspectives on the Treatment of Neuroendocrine Tumors - Episode 10
CABINET Trial: Grade 3 Neuroendocrine Tumors
Panelists discuss how cabozantinib showed promising activity in the challenging well-differentiated grade 3 neuroendocrine tumor (NET) population (around 25% response rate), offering a nonchemotherapy option for these aggressive tumors that often lack uniform somatostatin receptor expression.
Pancreatic NET Cohort Results and Treatment Implications
The pancreatic NET cohort in CABINET included approximately 95 patients in a 2:1 randomized design, showing robust efficacy with median progression-free survival of 13.8 months vs 4.4 months for placebo. The patient population reflected clinical practice diversity, with 60% grade 2, 23% grade 1, and inclusion of well-differentiated grade 3 tumors. Nearly all patients had received somatostatin analogs, with significant proportions having received peptide receptor radionuclide therapy (50%) and everolimus (80%).
Notably, 20% to 30% of patients had prior sunitinib exposure, providing unique data on tyrosine kinase inhibitor (TKI) activity following previous TKI therapy. The impressive 18% to 19% radiographic response rate substantially exceeded previous TKI response rates, suggesting enhanced activity profiles. Some differences in toxicity emerged, including slightly higher thromboembolic events in pancreatic patients, possibly related to the inherent higher thrombotic risk in pancreatic NETs.
Treatment sequencing decisions remain challenging, with cabozantinib approval extending beyond the heavily pretreated trial population to include earlier-line use. Community oncologists’ familiarity with cabozantinib from other indications (renal cell carcinoma, thyroid cancer) may facilitate adoption. The drug’s activity across grade 1 to 3 well-differentiated tumors provides flexibility for diverse patient presentations requiring individualized treatment approaches.
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