de Mestier Louis, Lamarca Angela, Hernando Jorge, Zandee Wouter, Alonso-Gordoa Teresa, Perrier Marine, Walenkamp Annemiek Me, Chakrabarty Bipasha, Landolfi Stefania, Van Velthuysen Marie-Louise F, Kats-Ugurlu Gursah, Caminoa Alejandra, Ronot Maxime, Manoharan Prakash, Garcia-Alvarez Alejandro, Brabander Tessa, García Gómez-Muriel María Isabel, Cadiot Guillaume, Couvelard Anne, Capdevila Jaume, Pavel Marianne E, Cros Jérôme
Université de Paris, Department of Gastroenterology-Pancreatology, Beaujon University Hospital (APHP), Clichy, France.
Division of Cancer Sciences, Department of Medical Oncology, The Christie NHS Foundation, University of Manchester, Manchester, United Kingdom.
Endocr Relat Cancer. 2021 Jun 23;28(8):549-561. doi: 10.1530/ERC-21-0109.
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.
对于3级神经内分泌肿瘤（G3 NETs），目前尚无标准化治疗方案。我们旨在描述晚期G3 NETs患者接受的治疗方法，并比较其疗效。对2010年至2018年期间在七个专家中心接受治疗的晚期消化系G3 NETs患者进行了回顾性研究。病理样本进行集中审查，放射学数据进行本地审查。我们分析了一线（L1）或二线（L2）治疗获得的根据实体瘤疗效评价标准（RECIST）定义的客观缓解率（OR）、肿瘤生长率（TGR）和无进展生存期（PFS）。我们纳入了74例晚期G3 NETs患者，大多数起源于十二指肠或胰腺（71.6%），Ki-67中位数为30%。126次治疗（L1 = 74；L2 = 52）包括基于烷化剂的化疗（n = 32）、依托泊苷-铂化疗（n = 22）或腺癌样化疗（n = 20）、生长抑素类似物（n = 21）、靶向治疗（n = 22）和肝脏定向治疗（n = 7）。与其他治疗相比，基于烷化剂的化疗达到了最高的OR率（37.9%）（多变量OR 4.22，95%置信区间（1.5 - 12.2）；P = 0.008）。腺癌样化疗和基于烷化剂的化疗在3个月时TGR降低最为显著（分别为P < 0.001和P = 0.008）。腺癌样化疗（16.5个月（9.0 - 24.0））和靶向治疗（12.0个月（8.2 - 15.8））获得了最长的中位PFS，而生长抑素类似物（6.2个月（3.8 - 8.5））和依托泊苷-铂化疗（7.2个月（5.2 - 9.1））的PFS最短。依托泊苷-铂化疗的PFS短于腺癌样化疗（多变量风险比3.69（1.61 - 8.44），P = 0.002）和基于烷化剂的化疗（多变量风险比1.95（1.01 - 3.78），P = 0.049）。总体而言，就OR和PFS而言，腺癌样化疗和基于烷化剂的化疗可能是晚期G3 NETs患者最有效的治疗方法。在这种情况下依托泊苷-铂化疗疗效不佳。
