FDA Approves Cabometyx, Another Treatment for Neuroendocrine Tumors

With the recent approval by the U.S. Food and Drug Administration (FDA) of Cabometyx (cabozantinib) for the treatment of patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET) and well-differentiated extra-pancreatic neuroendocrine tumors (epNET), another treatment option has become available to patients, as Dr. Jennifer Chan explained to CURE.

“We have long needed more options to treat advanced NETs. Despite the advances that have been made in recent years, patients will at some point have disease growth that warrants additional therapy. To now have [Cabometyx (cabozantinib)] as a standard option, provides us with more tools to control disease,” said Chan.

The effectiveness of Cabometyx for patients with NETs was determined in the phase 3 CABINET trial of patients with pNET and epNET. Chan, clinical director of the Gastrointestinal Cancer Center and director of the Program in Carcinoid and Neuroendocrine Tumors at Dana-Farber Cancer Institute in Boston, led the trial.

She spoke with CURE about Cabometyx, the findings of the CABINET trial, unmet needs that persist and more.

CURE: For patients, what is the significance of this FDA approval?

Chan: I think the main significance is having another option for treatment. We have long needed more options to treat advanced NETs. Despite the advances that have been made in recent years, patients will at some point have disease growth that warrants additional therapy. To now have [Cabometyx (cabozantinib)] as a standard option provides us with more tools to control disease.

This is particularly relevant for patients with extra-pancreatic NETs. We have not had an approved tyrosine kinase inhibitor to treat extra-pancreatic NETs, and this approval opens up a new category of therapy for this patient population. The approval also extends to patients with rare primary tumor sites, for example thymus, that have not been included with other approvals.

Can you tell me a bit about the study findings that supported this approval?

The study that led to the approval was a phase 3 trial conducted in patients with advanced NETs, all of whom had disease that had progressed after at least one prior line of therapy. The trial had two independent cohorts: one group of patients with pancreatic NETs and the other with NETs originating outside the pancreas (epNET). It was a randomized trial comparing Cabometyx, starting at a dose of 60 milligrams a day, to placebo. The primary outcome of the study was to assess progression-free survival.

What the researchers observed in both groups was that Cabometyx significantly improved progression-free survival compared with placebo. Specifically, there was a 62% reduction in the risk of disease progression or death in patients with epNET, and a 77% reduction in the risk of disease progression or death in those with pNETs. This provided clear evidence that Cabometyx can slow disease progression and control tumor growth. Based on this demonstrated effectiveness, the drug was approved, adding another treatment option for patients.

It’s important to note that there are multiple therapies that can be considered for patients with advanced NET. We can choose which option to use based on each person's individual situation and the specific characteristics of their disease. The good news is that with the approval of [Cabometyx], there is another standard therapy for patients and their providers to consider. 

What unmet needs persist for patients?

There is a need to understand what the best option is for patients and how to sequence therapy. Having a better sense of what the predictors of benefit are for [Cabometyx] — as well as other treatments — will help with treatment selection for individual patients. There is also a need for clinical trials that involve head-to-head comparisons of agents, one versus the other, to help us understand how the effectiveness and side-effects of different agents compare to each other. There is also a need for treatments that are effective but have a better side effect profile.

What is the side effect profile like?

[Cabometyx] is a tyrosine kinase inhibitor. It is an agent that inhibits multiple receptors, including the vascular endothelial growth factor receptor. One of the main side effects of [Cabometyx] is hypertension. It can also cause diarrhea and fatigue. In the trial, we also observed thromboembolic events in patients with pancreatic NETs. These are known side effects of [Cabometyx] that have been observed when the drug has been used to treat other cancer types. We also need to monitor for these side effects and adjust treatment doses as needed in patients with NETs.

Transcript has been edited for clarity and conciseness.

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