Improved survival with higher doses of octreotide long-acting release in gastroenteropancreatic neuroendocrine tumors

Gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) represent a heterogeneous group of tumors that is associated with an indolent course. Octreotide has a positive effect on disease stabilization in well-differentiated midgut NETs, but a meaningful survival analysis was not possible due to insufficient events. Higher doses of octreotide long-acting release (LAR) are often used in clinical practice for control of carcinoid symptoms and our objective was to determine if dose of octreotide correlates with survival. We reviewed all patients with advanced GEP NETs who initiated treatment with octreotide LAR between 2000 and 2013 in a large, representative Canadian province. We compared overall survival in patients who received low (< 30 mg) compared to high (≥ 30 mg) doses of octreotide. A total of 170 patients were identified. Baseline characteristics in the low- and high-dose groups were similar: median age 62/63 years, 50/58% were male, 46/48% originated from the small bowel, and 74/66% had liver metastases at diagnosis. The median time from diagnosis to treatment initiation was 5.5 and 6.0 months. Octreotide LAR was initiated with the intent of symptom management (71%), disease stabilization (23%), or biomarker control (6%). Median overall survival (OS) was better in the high-dose group, 66 months compared to 22 months (multivariate HR 0.5, p < 0.01). Age ≥ 65 (HR 1.9, p < 0.01), ECOG ≥ 2 (HR 2.7, p < 0.01), and pancreatic NETs (HR 1.7, p = 0.03) were all predictors of worse survival. Our findings suggest that octreotide may confer survival benefits in GEP NETs. Further prospective studies are warranted to validate the impact of high-dose octreotide on outcomes.