Pazopanib Plus Octreotide Active in Patients With Advanced Well-Differentiated Pancreatic Neuroendocrine Tumors
In a phase II study reported in The Lancet Oncology, Phan et al found that the VEGFR-1, -2, -3 inhibitor pazopanib (Votrient) plus depot octreotide produced responses in patients with advanced well-differentiated neuroendocrine tumors. No responses were observed in patients with carcinoid tumors.
Study Details
The study included 32 patients with pancreatic neuroendocrine tumors and 20 patients with carcinoid tumors treated at MD Anderson Cancer Center or Dana-Farber Cancer Institute. Patients received pazopanib 800 mg once daily; those already receiving octreotide continued on the same dose, and those who had not been receiving octreotide received a standard dose of 30 mg by intramuscular injection every 28 days.
Response Rates
Among patients with pancreatic neuroendocrine tumors, objective response was observed in seven (21.9%, 95% confidence interval [CI] = 11.0%–38.8%). No responses were observed in the first 20 patients with carcinoid tumors, with accrual thus being terminated. The response rate among 21 pancreatic neuroendocrine tumor patients with progressive disease at study entry was 28.6%. Responses were observed only among the 26 patients with liver metastases.
Patients with pancreatic neuroendocrine tumors had a median progression-free survival of 14.4 months (95% CI = 5.9–22.9 months) and a median overall survival of 25 months (95% CI = 15.5–34.4 months). Patients with carcinoid tumors had a median progression-free survival of 12.2 months (95% CI = 5.3–19.0 months) and a median overall survival of 18.5 months (95% CI = 15.0–22.0 months).
The most common adverse events of any grade were fatigue (75%), nausea (63%), diarrhea (63%), and hypertension (54%). The most common grade 3 adverse events were hypertension (12%), fatigue (8%), diarrhea (6%), increased alanine transaminase levels (6%), increased aspartate transaminase levels (6%), and neutropenia (6%). One patient had grade 4 hypertriglyceridemia, and one had grade 4 thrombosis.
The investigators concluded: “Treatment with pazopanib is associated with tumor response for patients with pancreatic [neuroendocrine tumors] but not for carcinoid tumors; a randomized controlled phase 3 study to assess pazopanib in advanced pancreatic [neuroendocrine tumors] is warranted.”
James C. Yao, MD, of The University of Texas MD Anderson Cancer Center, is the corresponding author of The Lancet Oncology article.
The study was funded by the National Cancer Institute. For full disclosures of the study authors, visit www.thelancet.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
