New Frontiers in Neuroendocrine Tumors (NETs): Treatment Advances and Insights From the Phase 3 CABINET Study - Episode 7
Integrating Cabozantinib Into the NET Treatment Landscape
Panelists discuss cabozantinib’s role in the neuroendocrine tumor treatment landscape, emphasizing its utility as a third-line option post somatostatin analogues and systemic therapy, while highlighting its efficacy in heavily pretreated patients, the importance of careful sequencing—especially relative to PRRT—and considerations for ideal patient selection, including those with grade 3 well-differentiated tumors.
Cabozantinib’s approval through the CABINET trial has added an important tool to the neuroendocrine tumor (NET) treatment landscape. Most clinicians agree it is best positioned as a third-line therapy, following progression on somatostatin analogues (SSAs) and another systemic agent such as everolimus, peptide receptor radionuclide therapy (PRRT), or chemotherapy. Though not typically used in the first line, there are scenarios where earlier use could be justified based on patient-specific factors such as comorbidities or lack of access to other therapies. One of the key takeaways from the trial is its demonstrated efficacy even in heavily pretreated patients—making it a viable option late in the treatment sequence. However, real-world logistics such as insurance coverage and toxicity management also play critical roles in determining when it is used.
In terms of sequencing, PRRT will likely continue to precede cabozantinib for most patients. The preference for PRRT is due to its favorable efficacy, tolerability, and durable responses. That said, cabozantinib offers a compelling alternative post PRRT or in patients who may not be ideal PRRT candidates. Importantly, clinicians must weigh disease volume, symptom burden, and bone marrow reserve when sequencing these agents. There is also ongoing debate about continuing SSAs after progression in nonfunctioning tumors. While data from the CABINET trial show that up to 50% of patients remained on SSAs despite progression, this remains a clinical gray zone, with decisions often tailored to individual circumstances.
The ideal candidate for cabozantinib is a nonsyndromic, grade 2 NET patient who has progressed after at least 1 prior line beyond SSAs. Patients with functional tumors, especially those with baseline diarrhea from carcinoid syndrome, may require extra caution, as cabozantinib can exacerbate gastrointestinal symptoms. Notably, the drug is a valuable option for grade 3 well-differentiated NETs, for which few therapies exist, and where CABINET provides rare efficacy data.
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