Pusceddu Sara, Vernieri Claudio, Di Maio Massimo, Prinzi Natalie, Torchio Martina, Corti Francesca, Coppa Jorgelina, Buzzoni Roberto, Di Bartolomeo Maria, Milione Massimo, Regnault Benjamin, Truong Thanh Xuan-Mai, Mazzaferro Vincenzo, de Braud Filippo
Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori (ENETS Center of Excellence), 20133 Milan, Italy.
IFOM, The FIRC Institute of Molecular Oncology, 20139 Milan, Italy.
Cancers (Basel). 2021 Dec 23;14(1):69. doi: 10.3390/cancers14010069.
The prognostic role of diabetes mellitus (DM) in advanced enteropancreatic neuroendocrine tumors (NETs) is unclear. Progression free survival (PFS) was assessed in post-hoc analyses of the 96-week, phase III, double-blind, placebo-controlled CLARINET study of lanreotide 120 mg in patients with advanced non-functional enteropancreatic NETs with DM (with/without metformin) and without DM. Of 204 patients, there were 79 with DM (lanreotide, 42 {metformin, 14}; placebo, 37 {metformin, 10}) and 125 without DM (lanreotide, 59; placebo, 66). Median PFS was 96.0 and 98.0 weeks with and without DM, respectively (hazard ratio 1.20 {95% confidence interval 0.79 to 1.82}; = 0.380). No difference in PFS was observed in lanreotide-treated patients with/without DM ( = 0.8476). In the placebo group, median PFS was numerically shorter with versus without DM ( = 0.052) and was significantly longer in patients with DM and metformin (85.7 weeks) versus without metformin (38.7 weeks; = 0.009). Multivariable Cox analyses showed that DM at baseline was not associated with PFS ( = 0.079); lanreotide was significantly associated with lower disease progression risk ( = 0.017). Lanreotide efficacy was confirmed in patients with advanced enteropancreatic NETs, regardless of diabetic status; DM was not a negative prognostic factor. A potential antitumor effect of metformin was observed in patients receiving placebo.
糖尿病（DM）在晚期胃肠胰神经内分泌肿瘤（NETs）中的预后作用尚不清楚。在一项关于120mg兰瑞肽用于晚期无功能胃肠胰NETs伴DM（使用/未使用二甲双胍）和不伴DM患者的96周、III期、双盲、安慰剂对照的CLARINET研究的事后分析中，评估了无进展生存期（PFS）。204例患者中，79例伴DM（兰瑞肽组42例{使用二甲双胍14例}；安慰剂组37例{使用二甲双胍10例}），125例不伴DM（兰瑞肽组59例；安慰剂组66例）。伴DM和不伴DM患者的中位PFS分别为96.0周和98.0周（风险比1.20{95%置信区间0.79至1.82}；P = 0.380）。在接受兰瑞肽治疗的伴/不伴DM患者中未观察到PFS有差异（P = 0.8476）。在安慰剂组中，伴DM患者的中位PFS在数值上短于不伴DM患者（P = 0.052），且伴DM且使用二甲双胍的患者（85.7周）的PFS显著长于未使用二甲双胍的患者（38.7周；P = 0.009）。多变量Cox分析显示基线时DM与PFS无关（P = 0.079）；兰瑞肽与较低的疾病进展风险显著相关（P = 0.017）。无论糖尿病状态如何，兰瑞肽在晚期胃肠胰NETs患者中均证实有效；DM不是不良预后因素。在接受安慰剂治疗的患者中观察到二甲双胍有潜在的抗肿瘤作用。
