Placebo-Controlled, Double-Blind, Prospective, Randomized Study Of The Effect Of Octreotide Lar In The Control Of Tumor Growth In Patients With Metastatic Neuroendocrine Midgut Tumors: A Report From The Promid Study Group

4508 Background: Octreotide is currently used for the control of symptoms in patients with gastroenteropancreatic neuroendocrine tumors (NETs). However, the ability of long-acting somatostatin analogues to control the growth of well-differentiated metastatic NETs is a matter of debate. The analysis of the first randomized, double-blind, placebo-controlled, multicenter, phase IIIb study of octreotide LAR in patients with metastatic NETs of the midgut is presented. Methods: Treatment-naïve patients with histologically confirmed locally inoperable or metastasized well-differentiated NETs and a Karnofsky index >60 were randomized to receive either octreotide LAR 30 mg/month (mo) or placebo for 18 mos, or until tumor progression or death. The primary endpoint was median time to tumor progression. Secondary endpoints included objective tumor response rate (WHO criteria), measured every 3 mos, as well as symptom control and overall survival. This was a planned interim analysis using the Lan-DeMets error spending approach. Results: Eighty-five patients (n=43 octreotide LAR; n=42 placebo) have been enrolled to date and data from 67 patients with tumor progressions and 16 deaths (n=7 octreotide LAR; n=9 placebo) are included here. Median time to tumor progression in the octreotide LAR and placebo groups were 14.3 mos and 6 mos, respectively (HR: 0.34; 95% CI: 0.20–0.59; P=0.000072). After 6 mos of treatment, stable disease was seen in 67% and 37.2% of patients treated with octreotide LAR and placebo, respectively. Due to the low number of observed deaths, median survival time could not be estimated. Conclusions: Octreotide LAR significantly lengthens median time to tumor progression compared with placebo in patients with metastatic NETs of the midgut. Patients treated with octreotide LAR had a 66% risk reduction of tumor progression compared with patients receiving placebo. Octreotide LAR demonstrates substantial tumor control and shows a more favorable antiproliferative response than placebo as two-thirds of patients treated with octreotide LAR achieved stable disease at 6 mos. [Table: see text]