Cabozantinib Active in Carcinoid Tumors and Pancreatic NETs

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.

Patients with advanced carcinoid tumors (n = 41) or pancreatic NETs (n = 20) were enrolled in parallel cohorts. Both groups received 60 mg of oral cabozantinib daily and were restaged every 2 months for the first 6 months, and then every 3 months.

The median progression-free survival (PFS) was 21.8 months (95% CI, 8.5-23.0) in the pancreatic NET cohort and 31.4 months (95% CI, 8.5-NR) in the carcinoid tumor cohort. Partial responses were observed in 6 patients with carcinoid NETs and 3 patients with pancreatic NETs, with an overall response rate of 15% in each group.

Grade 3/4 toxicities included hypertension (13%), hypophosphatemia (11%), diarrhea (10%), lymphopenia (7%), thrombocytopenia (5%), fatigue (5%), and increased lipase or amylase (8%). Overall, 81% of patients required a dose reduction.

These data support the evaluation of cabozantinib in a phase III trial and could lead to a new treatment option for patients with carcinoid tumors or pancreatic NETs who progress, according to lead study author Jennifer A. Chan, MD.

OncLive: Can you provide an overview of this trial?

In an interview with OncLive, 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.Chan: 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.

What mechanistic properties of cabozantinib suggest that there may be a benefit in this patient population?

Is a larger clinical trial included in the next steps?

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. 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. 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.

What is important to note for community physicians who may consider referring their patients to this trial?

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.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.