The CABINET trial: focus on lung NET patients

In this video, Dr Willem Lybaert, medical oncologist and NET expert at the VITAZ hospital and the University Hospital Antwerp, and Prof Ingel Demedts, pulmonologist and thoracic oncologist at the AZ Delta in Roeselare discuss the contemporary management of patients with pulmonary or thymic neuroendocrine tumors (NETs), with a particular focus on the results of the phase III CABINET trial in this subgroup of patients.

The CABINET trial is a pivotal phase III study evaluating the efficacy of cabozantinib, a multi-targeted tyrosine kinase inhibitor, compared with placebo in patients with advanced, well-differentiated neuroendocrine tumors (NETs) of gastroenteropancreatic or pulmonary origin. This heavily pretreated population included patients previously exposed to somatostatin analogues (SSAs), everolimus, peptide receptor radionuclide therapy (PRRT), and chemotherapy, thus reflecting a real-world scenario of treatment-resistant disease. The trial demonstrated that cabozantinib significantly improved progression-free survival (PFS) in both pancreatic and extra-pancreatic NET cohorts. 

A focused analysis of the lung and thymic NET subgroup, comprising approximately 50 patients, further supported the efficacy of cabozantinib. This group included two-thirds atypical and one-third typical pulmonary carcinoid tumors, all of which were heavily pretreated, with roughly 80% having received SSAs and everolimus. In this subgroup, cabozantinib extended median PFS to over 8 months, compared to just 2.7 months in the placebo arm, a statistically significant improvement with a favorable hazard ratio of 0.19 (95%CI: 0.06-0.54).

Cabozantinib was associated with notable grade 3 adverse events, including hypertension, diarrhea, hand-foot syndrome, fatigue, and gastrointestinal symptoms. As such, patient selection, close monitoring, and multidisciplinary management are essential, particularly given the fact that late-line NET patients often have declining performance status. Starting doses of cabozantinib may be individualized, with some clinicians initiating therapy at 40 mg daily in frail patients and escalating to the standard 60 mg as tolerated.

In the management of lung NETs, treatment sequencing remains multifaceted. SSAs remain the first-line option in patients with indolent disease and positive somatostatin receptor imaging. Everolimus and PRRT are also key therapeutic modalities, with PRRT gaining traction due to encouraging data in gastrointestinal and emerging data in thoracic NETs. Chemotherapy may be preferred in aggressive or rapidly progressive disease. Cabozantinib is thus positioned as a valuable later-line option following SSAs, everolimus, PRRT, or chemotherapy.