Two drugs show promise in advanced pancreatic neuroendocrine tumors

Sunitinib and everolimus improved progression-free survival in patients with advanced pancreatic neuroendocrine tumors, according to 2 recent studies.

In the first multinational study, 171 patients received either 37.5-mg sunitinib per day or placebo. Patients who received sunitinib had a median progression-free survival of 11.4 months compared with 5.5 months for those taking placebo (progression-free survival or death HR=0.42; 95% CI, 0.26–0.66; P<.001). There was an objective response rate of 9.3% in the sunitinib group and 0% in the placebo group. There were 9 deaths in the sunitinib group (10%) versus 21 deaths in the placebo group (25%) (HR=0.41; 95% CI, 0.19–0.89; P=.02). In the sunitinib group, the frequent adverse effects were diarrhea, nausea, vomiting, asthenia, and fatigue.  The study was discontinued early because there were more serious adverse events and deaths in the placebo group as well as a difference in progression-free survival favoring those receiving sunitinib.

The researchers conclude that continuous daily administration of 37.5 mg of sunitinib improved progression-free survival, overall survival, and the objective response rate compared to those patients receiving placebo with advanced pancreatic neuroendocrine tumors.

In the second multinational study, 410 patients either received 10 mg of everolimus once daily or placebo. For patients receiving everolimus, the median progression-free survival was 11.0 months compared with 4.6 months for those in the placebo group (HR=0.35; 95% CI, 0.27–0.45; P<.001). This represents a 65% reduction in the estimated risk of progression or death, note the authors. Estimates of the proportion of patients alive and progression-free at 18 months were 34% with everolimus as compared with 9% of those taking placebo.

Drug-related adverse events included stomatitis (in 64% of those receiving everolimus vs 17% in the placebo group); rash (49% vs 10%); diarrhea (34% vs 10%); fatigue (31% vs 14%); and infections (23% vs 6%). Infections were primarily upper respiratory. More serious adverse events included anemia (6% vs 0%) and hyperglycemia (5% vs 2%).

Compared to placebo, everolimus significantly prolonged progression-free survival among the study's patients and was associated with a low rate of severe adverse events, conclude the researchers.

Both studies appeared in the February 10, 2011 issue of The New England Journal of Medicine.