Multicenter, Observational Study of Lanreotide Autogel for the Treatment of Patients with Neuroendocrine Tumors in Routine Clinical Practice in Germany and Austria

Abstract

Background The long-acting somatostatin analog lanreotide autogel is effective in the treatment of patients with neuroendocrine tumors.

Objective To evaluate the long-term treatment response in patients with neuroendocrine tumors receiving lanreotide autogel in routine clinical practice.

Methods Non-interventional, 24-month study in patients with neuroendocrine tumors treated with lanreotide autogel (NCT01840449).

Results Patients (n=80) from 26 centers in Germany and Austria were enrolled. Neuroendocrine tumors were mainly grade 1/2, metastasized, intestinal, and associated with carcinoid syndrome; 88.9% had received previous neuroendocrine tumor treatment. Of those, 84.4% had previous surgery, 18.7% had received octreotide. The primary endpoint, defined by a <50% chromogranin A increase at month 12 compared with the lowest value between baseline and month 3 was achieved by 89.5% patients. Stable disease according to Response Evaluation Criteria in Solid Tumors 1.1 was observed in 76.9 and 75.0% patients at months 12 and 24 of lanreotide treatment, respectively. Mean change of chromogranin A levels from baseline to month 24 was −0.12 × upper limit of normal (95% CI, −0.22; −0.45). In a post hoc analysis, 38.5% of the subgroup of patients with carcinoid syndrome had daily diarrhea at baseline vs. 21.4% at month 24. At baseline, 27.8% of patients received lanreotide 120 mg every 4 weeks vs. 56.7% at month 24. Quality of life data were heterogeneous. No new safety issues arose and/or required further investigation.

Conclusions Our study reflects routine lanreotide autogel use in patients with advanced/metastatic neuroendocrine tumors. This analysis shows effectiveness with stabilization of disease-related symptoms and good tolerability of lanreotide autogel in clinical practice.

Key words

chromogranin A - carcinoid syndrome - diarrhea - flushing - quality of life

Publikationsverlauf

Eingereicht: 18. September 2020
Eingereicht: 07. Dezember 2020

Angenommen: 22. Dezember 2020

Artikel online veröffentlicht:
22. Juli 2021

• References

• 1 Dasari A, Shen C, Halperin D. et al. Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol 2017; 3: 1335-1342
• 2 Oberg KE. Gastrointestinal neuroendocrine tumors. Ann Oncol 2010; 21 Suppl 7 vii72-vii80
• 3 Pavel M, O'Toole D, Costa F. et al. ENETS consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site. Neuroendocrinology 2016; 103: 172-185
• 4 Grozinsky-Glasberg S, Grossman AB, Gross DJ. Carcinoid Heart Disease: From Pathophysiology to Treatment–'Something in the Way It Moves’. Neuroendocrinology 2015; 101: 263-273
• 5 Vinik AI, Wolin EM, Liyanage N. et al. Evaluation of lanreotide depot/Autogel efficacy and safety as a carcinoid syndrome treatment (ELECT): A randomized, double-blind, placebo-controlled trial. Endocr Pract 2016; 22: 1068-1080
• 6 O'Toole D, Ducreux M, Bommelaer G. et al. Treatment of carcinoid syndrome: A prospective crossover evaluation of lanreotide versus octreotide in terms of efficacy, patient acceptability, and tolerance. Cancer 2000; 88: 770-776
• 7 Fisher GA, Wolin EM, Liyanage N. et al. Lanreotide therapy in carcinoid syndrome: prospective analysis of patient-reported symptoms in patients responsive to prior octreotide therapy and patients naive to somatostatin analogue therapy in the ELECT phase 3 study. Endocr Pract 2018; 24: 243-255
• 8 Ruszniewski P, Valle JW, Lombard-Bohas C. et al. Patient-reported outcomes with lanreotide Autogel/Depot for carcinoid syndrome: An international observational study. Dig Liver Dis 2016; 48: 552-558
• 9 Ruszniewski P, Ish-Shalom S, Wymenga M. et al. Rapid and sustained relief from the symptoms of carcinoid syndrome: Results from an open 6-month study of the 28-day prolonged-release formulation of lanreotide. Neuroendocrinology 2004; 80: 244-251
• 10 Caplin ME, Pavel M, Cwikla JB. et al. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med 2014; 371: 224-233
• 11 Caplin ME, Pavel M, Cwikla JB. et al. Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: The CLARINET open-label extension study. Endocr Relat Cancer 2016; 23: 191-199
• 12 Somatuline Autogel EMA Summary of product characteristics. Ipsen Pharma GmbH, October 2018, https://www.ipsen.com/websites/Ipsen_Online/wp-content/uploads/sites/21/2019/12/11153003/Fachinformation_Somatuline-60_90_120-mg-Filmtabletten_Stand-Okt-2019.pdf
• 13 Somatuline Autogel US Prescribing Information. Ipsen Biopharmaceuticals, Inc, June 2019, https://www.ipsen.com/websites/Ipsen_Online/wp-content/uploads/2019/08/30162316/Somatuline_Depot_Full_Prescribing_Information_7.22.19.pdf
• 14 Pavel M, Unger N, Borbath I. et al. Safety and QOL in patients with Advanced NET in a phase 3b expanded access study of everolimus. Target Oncol 2016; 11: 667-675
• 15 Osoba D, Rodrigues G, Myles J. et al. Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol 1998; 16: 139-144
• 16 Singh S, Granberg D, Wolin E. et al. Patient-Reported Burden of a Neuroendocrine Tumor (NET) Diagnosis: Results From the First Global Survey of Patients With NETs. J Glob Oncol 2017; 3: 43-53
• 17 Basuroy R, Bouvier C, Ramage JK. et al. Presenting symptoms and delay in diagnosis of gastrointestinal and pancreatic neuroendocrine tumours. Neuroendocrinology 2018; 107: 42-49
• 18 de Herder WW, Hofland LJ, van der Lely AJ. et al. Somatostatin receptors in gastroentero-pancreatic neuroendocrine tumours. Endocr Relat Cancer 2003; 10: 451-458
• 19 Reubi JC, Laissue J, Waser B. et al. Expression of somatostatin receptors in normal, inflamed, and neoplastic human gastrointestinal tissues. Ann NY Acad Sci 1994; 733: 122-137
• 20 Dimitroulopoulos D, Xynopoulos D, Tsamakidis K. et al. Scintigraphic detection of carcinoid tumors with a cost effectiveness analysis. World J Gastroenterol 2004; 10: 3628-3633
• 21 Oberg K, Eriksson B. Nuclear medicine in the detection, staging and treatment of gastrointestinal carcinoid tumours. Best Pract Res Clin Endocrinol Metab 2005; 19: 265-276
• 22 Rinke A, Wiedenmann B, Auernhammer C. et al. S2k-Leitlinie Neuroendokrine Tumore, AWMF Register Nr. 021-26. Z Gastroenterol 2018; 56: 583-681
• 23 Cella D, Beaumont JL, Hudgens S. et al. Relationship between symptoms and health-related quality-of-life benefits in patients with carcinoid syndrome: Post Hoc Analyses From TELESTAR. Clin Ther 2018; 40: 2006-2020.e2002
• 24 Jiao X, Pulgar S, Boyd M. et al. Treatment patterns and clinical outcomes in patients with metastatic gastroenteropancreatic neuroendocrine tumors treated in the community practice setting in the United States. Pancreas 2018; 47: 173-182
• 25 Katznelson L, Laws ER, Melmed S. et al. Acromegaly: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2014; 99: 3933-3951
• 26 Pavel M, Valle JW, Eriksson B. et al. ENETS consensus guidelines for the standards of care in neuroendocrine neoplasms: Systemic therapy - biotherapy and novel targeted agents. Neuroendocrinology 2017; 105: 266-280