Jennifer A. Chan, MD
Cabozantinib (Cabometyx) demonstrated promising clinical activity in patients with carcinoid tumors and pancreatic neuroendocrine tumors (NETs) in a phase II trial.
, Chan, senior physician, clinical director, Program in Carcinoid and Neuroendocrine Tumors, Dana-Farber Cancer Institute, assistant professor of medicine, Harvard Medical School, discussed the significance of the phase II results of cabozantinib in patients with carcinoid tumors and pancreatic NETs.
OncLive: Can you provide an overview of this trial?
We conducted a phase II trial of cabozantinib in patients with advanced carcinoid and pancreatic NETs. There have been a lot of recent advances in the treatment of NETs, but there is still an unmet need for patients whose disease has progressed on available therapy.
There was some preclinical evidence to suggest that cabozantinib is active is NETs, so we evaluated it in both carcinoid [tumors] and pancreatic NETs. We are encouraged by the results that we saw; [cabozantinib] was associated with a response rate of 15% in the patients with pancreatic NETs, and a 15% response rate in patients with carcinoid NETs. We were also encouraged by the PFS durations that we observed, and there is going to be ongoing work to evaluate this in a larger trial. The toxicity profile with cabozantinib was consistent with the toxicities seen [with the drug] in clinical trials of other tumors.
What mechanistic properties of cabozantinib suggest that there may be a benefit in this patient population?
There is some evidence in NETs that suggest inhibition of MET may be an effective strategy. There are mouse models showing that activation of MET will lead to NET growth. There are also data to suggest that high levels of MET are associated with worse overall survival, and there are data in a mouse model suggesting that cabozantinib decreases metastases and invasion.
Is a larger clinical trial included in the next steps?
The larger trial is in the planning phases. We are planning to do a study through the Alliance [for Clinical Trials in Oncology], which will be a phase III trial of cabozantinib versus placebo in patients whose cancer has progressed on at least 1 line of therapy that includes everolimus (Afinitor). There is no limit to prior therapies.
The larger study is going to include both carcinoid [tumors] and pancreatic NETs, so we are hoping to evaluate activity in both of those diseases. The trial is specifically for patients whose cancer has progressed on everolimus, so at least the trial would evaluate the activity [of cabozantinib] in that group of patients who have had progression on everolimus.
What is important to note for community physicians who may consider referring their patients to this trial?
There are many patients whose cancer has progressed on the currently available therapies, or patients who are interested in more novel therapies. We have been very encouraged by the results that we have seen. Cabozantinib looks active in the study that we did, and we are optimistic that we can evaluate this in a larger study so that we can add this to the [list of] treatment options for these patients.
Chan JA, Faris JE, Murphy JE, et al. Phase II trial of cabozantinib in patients with carcinoid and pancreatic neuroendocrine tumors. In: Proceedings from the 10th Annual NANETS Symposium; October 19-21, 2017; Philadelphia, PA. Abstract 290.
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