TY - JOUR
T1 - Treatment outcomes of advanced digestive well-differentiated grade 3 NETs
AU - de Mestier, Louis
AU - Lamarca, Angela
AU - Hernando, Jorge
AU - Zandee, Wouter
AU - Alonso-Gordoa, Teresa
AU - Perrier, Marine
AU - Walenkamp, Annemiek M.E.
AU - Chakrabarty, Bipasha
AU - Landolfi, Stefania
AU - van Velthuysen, Marie Louise F.
AU - Kats-Ugurlu, Gursah
AU - Caminoa, Alejandra
AU - Ronot, Maxime
AU - Manoharan, Prakash
AU - Garcia-Alvarez, Alejandro
AU - Brabander, Tessa
AU - Gómez-Muriel, María Isabel García
AU - Cadiot, Guillaume
AU - Couvelard, Anne
AU - Capdevila, Jaume
AU - Pavel, Marianne E.
AU - Cros, Jérôme
N1 - Funding Information:
NET CONNECT is supported by an 阀ndependent Educational Grant from 阀PSEN. The program is, therefore, independent, and the content is not influenced by 阀PSEN and is under the sole responsibility of the authors. Dr Louis de Mestier was part-funded by the Société Nationale Française de Gastro-Entérologie. Dr Angela Lamarca was part-funded by The Christie Charity.
Publisher Copyright:
© 2021 BioScientifica Ltd.. All rights reserved.
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85109354560&partnerID=8YFLogxK
U2 - 10.1530/ERC-21-0109
DO - 10.1530/ERC-21-0109
M3 - Review article
C2 - 34061764
AN - SCOPUS:85109354560
SN - 1351-0088
VL - 28
SP - 549
EP - 561
JO - Endocrine-Related Cancer
JF - Endocrine-Related Cancer
IS - 8
ER -
