CABINET Trial: Pancreatic Neuroendocrine Tumors Cohort

CABINET Trial Design and Nonpancreatic Results

The CABINET study enrolled nearly 300 patients in a large, well-designed, randomized, double-blind, placebo-controlled trial. The nonpancreatic NET cohort included approximately 200 patients with predominantly well-differentiated grade 1 to 2 tumors, representing the typical patient population seen in clinical practice. These were heavily pretreated patients who had received prior somatostatin analogs, with majority having received peptide receptor radionuclide therapy and everolimus.

The primary end point showed dramatic improvement in progression-free survival: over 8 months with cabozantinib vs approximately 3 months with placebo. This substantial difference occurred in a heavily pretreated population, demonstrating significant drug activity even after multiple prior therapies. Response rates in nonpancreatic tumors were modest but meaningful, reflecting the typically more indolent biology of these tumors compared to pancreatic primaries.

Toxicity management proved crucial, with the average dose during the trial approximately 40 mg daily despite the 60-mg starting dose and label recommendation. This dose reduction pattern maintains efficacy while improving tolerability, with evidence suggesting activity even at 20 mg daily. The key insight involves recognizing that dose reductions don’t necessarily compromise antitumor activity while significantly improving patient quality of life.