Leonidas Nikolaos Diamantopoulos1, Faidon-Marios Laskaratos2, Markos Kalligeros3, Ruchir Shah2, Shaunak Navalkissoor2, Gopinath Gnanasegaran2, Jamie Banks2, Jack Smith2, Benjamin Jacobs2, Michail Galanopoulos4, Dalvinder Mandair2, Martyn Caplin2, Christos Toumpanakis5. 1. Division of Oncology, Department of Medicine, University of Washington, Seattle Cancer Care Alliance, Seattle, Washington, USA. 2. Neuroendocrine Tumour Unit, Centre for Gastroenterology, ENETS Centre of Excellence, Royal Free London NHS Foundation Trust and University College London, London, United Kingdom. 3. Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA. 4. Department of Gastroenterology, 401 General Military Hospital, Athens, Greece. 5. Neuroendocrine Tumour Unit, Centre for Gastroenterology, ENETS Centre of Excellence, Royal Free London NHS Foundation Trust and University College London, London, United Kingdom, c.toumpanakis@ucl.ac.uk.
Abstract
BACKGROUND: 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-NET cohort. METHODS: Patients with advanced GEP-NET, treated with long-acting release (LAR) octreotide 30 mg or lanreotide Autogel 120 mg 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: The 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 cases (55%) and 30/55 cases (55%) with available data, respectively. The 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, a Ki-67 index ≥5% and multiple extrahepatic metastases were independently associated with inferior PFS. CONCLUSIONS: Above-label doses of SSAs may offer a considerable prolongation of PFS and could be utilized as a bridge to other more toxic treatments. Patients with small bowel/colorectal primaries, a Ki-67 index <5% and absence of/limited extrahepatic metastases are more likely to benefit from this approach.
BACKGROUND: 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-NET cohort. METHODS: Patients with advanced GEP-NET, treated with long-acting release (LAR) octreotide 30 mg or lanreotide Autogel 120 mg 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: The 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 cases (55%) and 30/55 cases (55%) with available data, respectively. The 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, a Ki-67 index ≥5% and multiple extrahepatic metastases were independently associated with inferior PFS. CONCLUSIONS: Above-label doses of SSAs may offer a considerable prolongation of PFS and could be utilized as a bridge to other more toxic treatments. Patients with small bowel/colorectal primaries, a Ki-67 index <5% and absence of/limited extrahepatic metastases are more likely to benefit from this approach.
Authors: Tim Meyer; Martyn Caplin; Mohid S Khan; Christos Toumpanakis; Shishir Shetty; John K Ramage; Aude Houchard; Kate Higgs; Tahir Shah Journal: J Neuroendocrinol Date: 2022-02-07 Impact factor: 3.870
Authors: Barbara Bober; Marek Saracyn; Maciej Kołodziej; Łukasz Kowalski; Elżbieta Deptuła-Krawczyk; Waldemar Kapusta; Grzegorz Kamiński; Olga Mozenska; Jacek Bil Journal: Clin Med Insights Cardiol Date: 2020-10-27