Treatment outcomes of advanced digestive well-differentiated grade 3 NETs

in Endocrine-Related Cancer
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  • 1 Université de Paris, Department of Gastroenterology-Pancreatology, Beaujon University Hospital (APHP), Clichy, France
  • 2 Division of Cancer Sciences, Department of Medical Oncology, The Christie NHS Foundation, University of Manchester, Manchester, United Kingdom
  • 3 Department of Medical Oncology, Vall d’Hebron University Hospital and Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain
  • 4 Department of Internal Medicine, Sector Endocrinology, Erasmus University Medical Center and Erasmus MC Cancer Institute, Rotterdam, The Netherlands
  • 5 Division of Endocrinology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  • 6 Department of Medical Oncology, Ramon y Cajal University Hospital, IRYCIS, Madrid, Spain
  • 7 Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré University Hospital, Reims, France
  • 8 Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
  • 9 Department of Pathology, The Christie, Manchester, United Kingdom
  • 10 Department of Pathology, Vall d’Hebron University Hospital, Barcelona, Spain
  • 11 Department of Pathology, Erasmus University Medical Center and Erasmus MC Cancer Institute, Rotterdam, The Netherlands
  • 12 Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  • 13 Department of Pathology, University Hospital Ramon y Cajal, Madrid, Spain
  • 14 Université de Paris, Department of Radiology, Beaujon University Hospital (APHP), Clichy, France
  • 15 Department of Radiology and Nuclear Medicine, The Christie, Manchester, United Kingdom
  • 16 Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
  • 17 Department of Radiology, University Hospital Ramon y Cajal, Madrid, Spain
  • 18 Université de Paris, Department of Pathology, Beaujon/Bichat University Hospital (APHP), Clichy/Paris, France
  • 19 Department of Endocrinology, Erlangen University Hospital, Erlangen, Germany

Correspondence should be addressed to L de Mestier: louisdemestier@hotmail.com
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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.

Supplementary Materials

    • Suppl. Figure S1. Tumor growth rate measured at baseline, at 3 months and at the time of RECIST-defined best response, depending on the treatment modality
    • Suppl. Figure S2. Overall survival (A) in the whole cohort, and (B) in the subgroup of 50 patients treated with first-line chemotherapy
    • Suppl. Table S1. Median Ki-67 index and baseline tumor growth rate for patients grouped by first-line therapy.
    • Suppl. Table S2. Multivariate analysis of baseline variables influencing the probability of objective response achieved by treatments received as first- or second-line for G3 neuroendocrine tumors
    • Suppl. Table S3. Multivariate analysis of baseline variables influencing the risk of death in 74 patients with advanced G3 neuroendocrine tumors

 

Society for Endocrinology

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