Elettra Merola1, Teresa Alonso Gordoa2, Panpan Zhang3, Taymeyah Al-Toubah4, Eleonora Pellè4, Agnieszka Kolasińska-Ćwikła5, Wouter Zandee6, Faidon Laskaratos7, Louis de Mestier8, Angela Lamarca9, Jorge Hernando10, Jaroslaw Cwikla11, Jonathan Strosberg4, Wouter de Herder6, Martin Caplin7, Mauro Cives12, Rachel van Leeuwaarde13. 1. Department of Gastroenterology, Azienda Provinciale per i Servizi Sanitari, Trento, Italy. 2. Medical Oncology Department. The Ramon y Cajal Health Research Institute, University Hospital Ramon y Cajal, Madrid, Spain. 3. Department of Early Drug Development Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China. 4. Moffitt Cancer Center, Tampa, Florida, USA. 5. Department of Oncology and Radiotherapy and Department of Radiology, Maria Skłodowska-Curie Memorial Cancer Center, 02-034, Warsaw, Poland. 6. Erasmus Medical Center and Erasmus MC Cancer Center, ENETS Centre of Excellence, Rotterdam, The Netherlands. 7. Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free London NHS Foundation Trust, London, United Kingdom. 8. Department of Gastroenterology and Pancreatology, ENETS Centre of Excellence, Beaujon Hospital and Université de Paris, Clichy, France. 9. The Christie NHS Foundation Trust, University of Manchester, Manchester, United Kingdom. 10. Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain. 11. University of Warmia and Mazury, Olsztyn, Poland. 12. Department of Biomedical Sciences and Human Oncology, University of Bari, Italy. 13. Department of Endocrine Oncology University Medical Center Utrecht, The Netherlands.
Abstract
BACKGROUND: Long-acting somatostatin analogs (SSAs) are the primary first-line treatment of well-differentiated advanced gastroenteropancreatic neuroendocrine tumors (NETs), but data about their efficacy in pancreatic NETs (panNETs) with Ki-67 ≥10% are still limited. MATERIALS AND METHODS: To assess the clinical outcomes of advanced, nonfunctioning, well-differentiated panNETs with Ki-67 ≥10% receiving first-line long-acting SSAs in a real-world setting, we carried out a retrospective, multicenter study including patients treated between 2014-2018 across 10 centers of the NET CONNECT Network. The primary endpoints were time to next treatment (TNT) and progression-free survival (PFS), whereas overall survival (OS) and treatment safety were secondary endpoints. RESULTS: A total of 73 patients were included (68 grade [G]2, 5 G3), with liver metastases in 61 cases (84%). After a median follow-up of 36.4 months (range, 6-173), the median TNT and PFS were 14.2 months (95% confidence interval [CI], 11.6-16.2) and 11.9 months (95% CI, 8.6-14.1) respectively. No statistically significant difference was observed according to the somatostatin analog used (octreotide vs. lanreotide), whereas increased tumor grade (hazard ratio [HR], 4.4; 95% CI, 1.2-16.6; p = .04) and hepatic tumor load (HR, 2; 95% CI, 1-4; p = .03) were independently associated with shortened PFS. The median OS recorded was 86 months (95% CI, 56.8-86 months), with poor outcomes observed when the hepatic tumor burden was >25% (HR, 3.4; 95% CI, 1.2-10; p = .01). Treatment-related adverse events were reported in 14 patients, most frequently diarrhea. CONCLUSION: SSAs exert antiproliferative activity in panNETs with Ki-67 ≥10%, particularly in G2 tumors, as well as when hepatic tumor load is ≤25%. IMPLICATIONS FOR PRACTICE: The results of the study call into question the antiproliferative activity of somatostatin analogs (SSAs) in pancreatic neuroendocrine tumors with Ki-67 ≥10%. Patients with grade 2 tumors and with hepatic tumor load ≤25% appear to derive higher benefit from SSAs. Prospective studies are needed to validate these results to optimize tailored therapeutic strategies for this specific patient population.
BACKGROUND: Long-acting somatostatin analogs (SSAs) are the primary first-line treatment of well-differentiated advanced gastroenteropancreatic neuroendocrine tumors (NETs), but data about their efficacy in pancreatic NETs (panNETs) with Ki-67 ≥10% are still limited. MATERIALS AND METHODS: To assess the clinical outcomes of advanced, nonfunctioning, well-differentiated panNETs with Ki-67 ≥10% receiving first-line long-acting SSAs in a real-world setting, we carried out a retrospective, multicenter study including patients treated between 2014-2018 across 10 centers of the NET CONNECT Network. The primary endpoints were time to next treatment (TNT) and progression-free survival (PFS), whereas overall survival (OS) and treatment safety were secondary endpoints. RESULTS: A total of 73 patients were included (68 grade [G]2, 5 G3), with liver metastases in 61 cases (84%). After a median follow-up of 36.4 months (range, 6-173), the median TNT and PFS were 14.2 months (95% confidence interval [CI], 11.6-16.2) and 11.9 months (95% CI, 8.6-14.1) respectively. No statistically significant difference was observed according to the somatostatin analog used (octreotide vs. lanreotide), whereas increased tumor grade (hazard ratio [HR], 4.4; 95% CI, 1.2-16.6; p = .04) and hepatic tumor load (HR, 2; 95% CI, 1-4; p = .03) were independently associated with shortened PFS. The median OS recorded was 86 months (95% CI, 56.8-86 months), with poor outcomes observed when the hepatic tumor burden was >25% (HR, 3.4; 95% CI, 1.2-10; p = .01). Treatment-related adverse events were reported in 14 patients, most frequently diarrhea. CONCLUSION: SSAs exert antiproliferative activity in panNETs with Ki-67 ≥10%, particularly in G2 tumors, as well as when hepatic tumor load is ≤25%. IMPLICATIONS FOR PRACTICE: The results of the study call into question the antiproliferative activity of somatostatin analogs (SSAs) in pancreatic neuroendocrine tumors with Ki-67 ≥10%. Patients with grade 2 tumors and with hepatic tumor load ≤25% appear to derive higher benefit from SSAs. Prospective studies are needed to validate these results to optimize tailored therapeutic strategies for this specific patient population.
Authors: Mei Sim Lung; Rodney J Hicks; Nick Pavlakis; Emma Link; Michael Jefford; Benjamin Thomson; David K Wyld; Winston Liauw; Timothy Akhurst; Narmatha Kuru; Michael Michael Journal: Asia Pac J Clin Oncol Date: 2020-02-07 Impact factor: 2.601
Authors: M Cives; M Ghayouri; B Morse; M Brelsford; M Black; A Rizzo; A Meeker; J Strosberg Journal: Endocr Relat Cancer Date: 2016-09 Impact factor: 5.678
Authors: Martyn E Caplin; Marianne Pavel; Jarosław B Ćwikła; Alexandria T Phan; Markus Raderer; Eva Sedláčková; Guillaume Cadiot; Edward M Wolin; Jaume Capdevila; Lucy Wall; Guido Rindi; Alison Langley; Séverine Martinez; Joëlle Blumberg; Philippe Ruszniewski Journal: N Engl J Med Date: 2014-07-17 Impact factor: 91.245
Authors: Ludovica Magi; Federica Mazzuca; Maria Rinzivillo; Giulia Arrivi; Emanuela Pilozzi; Daniela Prosperi; Elsa Iannicelli; Paolo Mercantini; Michele Rossi; Patrizia Pizzichini; Andrea Laghi; Alberto Signore; Paolo Marchetti; Bruno Annibale; Francesco Panzuto Journal: J Clin Med Date: 2019-06-25 Impact factor: 4.241
Authors: Karin Mayer; Selina Kiry; Anna Yordanova; Hojjat Ahmadzadehfar; Florian C Gaertner; Ralph A Bundschuh; Markus Essler; Maria A Gonzalez-Carmona; Christian P Strassburg; Hanno Matthaei; Philipp Lingohr; Savita Bisht; Peter Brossart; Georg Feldmann Journal: Int J Endocrinol Date: 2020-01-31 Impact factor: 3.257
Authors: Elettra Merola; Andrea Michielan; Umberto Rozzanigo; Marco Erini; Sandro Sferrazza; Stefano Marcucci; Chiara Sartori; Chiara Trentin; Giovanni de Pretis; Franca Chierichetti Journal: World J Gastrointest Surg Date: 2022-02-27