乌鸦传媒

PHILADELPHIA -- Treatment with cabozantinib was tied to objective tumor responses and promising progression-free survival (PFS) in patients with advanced carcinoid and pancreatic neuroendocrine tumors (pNET), researchers reported here.

With a daily cabozantinib (Cabometyx, Cometriq) treatment, 15% of 20 patients with pNET achieved partial response (95% CI 5-36%) and 75% achieved stable disease (95% CI 53-89%), which was the the trial's primary endpoint, according to Jennifer Chan, MD, MPH, of the Dana-Farber Cancer Institute in Boston, and colleagues.

In addition, 15% of 41 patients with carcinoid tumors achieved partial response (95% CI 7-28%) while 63% achieved stable disease with cabozantinib treatment (95% CI 48-76%), according to RECIST guidelines, they reported at the North American Neuroendocrine Tumor Society annual symposium.

"Cabozantinib is a tyrosine kinase inhibitor that targets multiple receptors that include MET, as well as the VEGF receptors AXL and RET," Chan explained. "It improves progression-free survival in patients with advanced renal cell carcinoma both in the first-line setting, as well as the second-line setting. It also is an approved treatment option for patients with advanced, progressive metastatic medullary thyroid carcinoma."

"In preclinical ENT models, cabozantinib has been shown to inhibit cell viability and decrease metastases and invasion," Chan's group wrote.

The , two-cohort trial included a total of 61 patients with either pNET or carcinoid, with unresectable or metastatic disease and radiographic disease progression within the year prior to enrollment. None of the participants had any previous exposure to cabozantinib, but they were on a stable dose of somatostatin analog for 2 months prior.

Among patients with carcinoid tumors, most had a primary tumor in the small intestine (71%), followed by lung (12%), or unknown location of the primary tumors (7%).

Participants with pNET reported prior therapies including sunitinib (Sutent, 60%), everolimus (Afinitor, 65%), as well as temozolomide (Temodar, 55%). Those with carcinoid tumors reported previously treatments including everolimus (29%), bevacizumab (Avastin, 15%), interferon (10%), and temozolomide (7%).

In 28-day cycles, the participants were administered an oral, daily dose of cabozantinib at 60 mg. During the first six treatment cycles, tumors were restaged after every two cycles. Beyond the first six cycles, restaging occurred after every three cycles. The pNET cohort completed a median of 10 treatment cycles, while the carcinoid cohort completed a median of eight cycles.

In regards to the trial's secondary endpoints, the pNET participants experienced a median PFS of 21.8 months (95% CI 8.5-32.0). Participants with carcinoid tumors had a median PFS of 31.4 months (95% CI 8.5-NR).

The "toxicity profile that we observed with cabozantinib is consistent with what's been observed in other disease settings," Chan stated. The most commonly reported adverse events included fatigue (67% of all grades), increase in aspartate aminotransferase (59%), and diarrhea (54%).

"A randomized phase III trial to confirm activity of cabozantinib in carcinoid and pancreatic NET is in development," the authors concluded.

Comment