JOURNAL ARTICLE

Antiproliferative Effect Of Above-Label Doses Of Somatostatin Analogs For The Management Of Gastroenteropancreatic Neuroendocrine Tumors

Leonidas Diamantopoulos, Faidon-Marios Laskaratos, Markos Kalligeros, Ruchir Shah, Shaunak Navalkissoor, Gopinath Gnanasegaran, Jamie Banks, Jack Smith, Benjamin Jacobs, Michail Galanopoulos, Dalvinder Mandair, Martyn Caplin, Christos Toumpanakis
Neuroendocrinology 2020 June 15
32541155

INTRODUCTION: Above-label doses of somatostatin analogs (SSAs) are increasingly utilized in the management of inoperable/metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs), progressing on standard 4-weekly regimens.

OBJECTIVE: To evaluate the antiproliferative effect of 3-weekly SSA administration in a retrospective GEP-NETs cohort.

METHODS: Patients with advanced GEP-NETs, treated with long acting release (LAR) octreotide 30mg or lanreotide Autogel 120mg at a 3-weekly interval, after disease progression on standard 4-weekly doses, were retrospectively identified. Clinicopathologic and treatment response data were collected. Progression-free survival (PFS - dose escalation to radiographic progression or death) was estimated with the Kaplan - Meier method. Factors associated with PFS were identified with the Cox proportional-hazards model.

RESULTS: Inclusion criteria were fulfilled by 105 patients. Octreotide LAR was administered to 60 (57%) and lanreotide Autogel to 45 (43%). Indications for dose escalation were breakthrough carcinoid symptoms (58%), radiographic progression (35%) and/or increasing biomarkers (11%). Diarrheal and/or flushing symptomatic improvement was identified in 37/67 (55%) and 30/55 cases (55%) with available data, respectively. Disease control rate (radiographic partial response or stable disease) was achieved in 53 patients (50%). Median PFS was 25.0 months (95% CI: 16.9 - 33.1). Patients with radiographic progression <12 months from 4-weekly SSA initiation had worse PFS after dose escalation (7.0 vs. 17.0 months, p = 0.002). In multivariate analysis, pancreatic NETs, Ki-67≥5% and multiple extrahepatic metastases were independently associated with inferior PFS.

CONCLUSIONS: Above-label doses of SSAs may offer a considerable prolongation in PFS and could be utilized as a bridge to other more toxic treatments. Patients with small bowel/colorectal primaries, Ki-67<5% and absence of/limited extrahepatic metastases are more likely to benefit from this approach.

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