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  • Author: María Isabel García Gómez-Muriel x
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Louis de Mestier Université de Paris, Department of Gastroenterology-Pancreatology, Beaujon University Hospital (APHP), Clichy, France

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Angela Lamarca Division of Cancer Sciences, Department of Medical Oncology, The Christie NHS Foundation, University of Manchester, Manchester, United Kingdom

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Jorge Hernando Department of Medical Oncology, Vall d’Hebron University Hospital and Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain

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Wouter Zandee Department of Internal Medicine, Sector Endocrinology, Erasmus University Medical Center and Erasmus MC Cancer Institute, Rotterdam, The Netherlands
Division of Endocrinology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

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Teresa Alonso-Gordoa Department of Medical Oncology, Ramon y Cajal University Hospital, IRYCIS, Madrid, Spain

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Marine Perrier Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré University Hospital, Reims, France

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Annemiek ME Walenkamp Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands

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Bipasha Chakrabarty Department of Pathology, The Christie, Manchester, United Kingdom

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Stefania Landolfi Department of Pathology, Vall d’Hebron University Hospital, Barcelona, Spain

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Marie-Louise F Van Velthuysen Department of Pathology, Erasmus University Medical Center and Erasmus MC Cancer Institute, Rotterdam, The Netherlands

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Gursah Kats-Ugurlu Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

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Alejandra Caminoa Department of Pathology, University Hospital Ramon y Cajal, Madrid, Spain

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Maxime Ronot Université de Paris, Department of Radiology, Beaujon University Hospital (APHP), Clichy, France

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Prakash Manoharan Department of Radiology and Nuclear Medicine, The Christie, Manchester, United Kingdom

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Alejandro Garcia-Alvarez Department of Medical Oncology, Vall d’Hebron University Hospital and Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain

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Tessa Brabander Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands

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María Isabel García Gómez-Muriel Department of Radiology, University Hospital Ramon y Cajal, Madrid, Spain

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Guillaume Cadiot Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré University Hospital, Reims, France

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Anne Couvelard Université de Paris, Department of Pathology, Beaujon/Bichat University Hospital (APHP), Clichy/Paris, France

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Jaume Capdevila Department of Medical Oncology, Vall d’Hebron University Hospital and Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain

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Marianne E Pavel Department of Endocrinology, Erlangen University Hospital, Erlangen, Germany

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Jérôme Cros Université de Paris, Department of Pathology, Beaujon/Bichat University Hospital (APHP), Clichy/Paris, France

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There is no standardized treatment for grade 3 neuroendocrine tumors (G3 NETs). We aimed to describe the treatments received in patients with advanced G3 NETs and compare their efficacy. Patients with advanced digestive G3 NETs treated between 2010 and 2018 in seven expert centers were retrospectively studied. Pathological samples were centrally reviewed, and radiological data were locally reviewed. We analyzed RECIST-defined objective response (OR), tumor growth rate (TGR) and progression-free survival (PFS) obtained with first- (L1) or second-line (L2) treatments. We included 74 patients with advanced G3 NETs, mostly from the duodenal or pancreatic origin (71.6%), with median Ki-67 of 30%. The 126 treatments (L1 = 74; L2 = 52) included alkylating-based (n = 32), etoposide-platinum (n = 22) or adenocarcinoma-like (n = 20) chemotherapy, somatostatin analogs (n = 21), targeted therapies (n = 22) and liver-directed therapies (n = 7). Alkylating-based chemotherapy achieved the highest OR rate (37.9%) compared to other treatments (multivariable OR 4.22, 95% CI (1.5–12.2); P = 0.008). Adenocarcinoma-like and alkylating-based chemotherapies showed the highest reductions in 3-month TGR (P < 0.001 and P = 0.008, respectively). The longest median PFS was obtained with adenocarcinoma-like chemotherapy (16.5 months (9.0–24.0)) and targeted therapies (12.0 months (8.2–15.8)), while the shortest PFS was observed with somatostatin analogs (6.2 months (3.8–8.5)) and etoposide-platinum chemotherapy (7.2 months (5.2–9.1)). Etoposide-platinum CT achieved shorter PFS than adenocarcinoma-like (multivariable HR 3.69 (1.61–8.44), P = 0.002) and alkylating-based chemotherapies (multivariable HR 1.95 (1.01–3.78), P = 0.049). Overall, adenocarcinoma-like and alkylating-based chemotherapies may be the most effective treatments for patients with advanced G3 NETs regarding OR and PFS. Etoposide-platinum chemotherapy has poor efficacy in this setting.

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