Merola Elettra, Alonso Gordoa Teresa, Zhang Panpan, Al-Toubah Taymeyah, Pellè Eleonora, Kolasińska-Ćwikła Agnieszka, Zandee Wouter, Laskaratos Faidon, de Mestier Louis, Lamarca Angela, Hernando Jorge, Cwikla Jaroslaw, Strosberg Jonathan, de Herder Wouter, Caplin Martin, Cives Mauro, van Leeuwaarde Rachel
Department of Gastroenterology, Azienda Provinciale per i Servizi Sanitari, Trento, Italy.
Medical Oncology Department. The Ramon y Cajal Health Research Institute, University Hospital Ramon y Cajal, Madrid, Spain.
Oncologist. 2021 Apr;26(4):294-301. doi: 10.1002/onco.13633. Epub 2020 Dec 29.
Long-acting somatostatin analogs (SSAs) are the primary first-line treatment of well-differentiated advanced gastroenteropancreatic neuroendocrine tumors (NETs), but data about their efficacy in pancreatic NETs (panNETs) with Ki-67 ≥10% are still limited.
To assess the clinical outcomes of advanced, nonfunctioning, well-differentiated panNETs with Ki-67 ≥10% receiving first-line long-acting SSAs in a real-world setting, we carried out a retrospective, multicenter study including patients treated between 2014-2018 across 10 centers of the NET CONNECT Network. The primary endpoints were time to next treatment (TNT) and progression-free survival (PFS), whereas overall survival (OS) and treatment safety were secondary endpoints.
A total of 73 patients were included (68 grade [G]2, 5 G3), with liver metastases in 61 cases (84%). After a median follow-up of 36.4 months (range, 6-173), the median TNT and PFS were 14.2 months (95% confidence interval [CI], 11.6-16.2) and 11.9 months (95% CI, 8.6-14.1) respectively. No statistically significant difference was observed according to the somatostatin analog used (octreotide vs. lanreotide), whereas increased tumor grade (hazard ratio [HR], 4.4; 95% CI, 1.2-16.6; p = .04) and hepatic tumor load (HR, 2; 95% CI, 1-4; p = .03) were independently associated with shortened PFS. The median OS recorded was 86 months (95% CI, 56.8-86 months), with poor outcomes observed when the hepatic tumor burden was >25% (HR, 3.4; 95% CI, 1.2-10; p = .01). Treatment-related adverse events were reported in 14 patients, most frequently diarrhea.
SSAs exert antiproliferative activity in panNETs with Ki-67 ≥10%, particularly in G2 tumors, as well as when hepatic tumor load is ≤25%.
The results of the study call into question the antiproliferative activity of somatostatin analogs (SSAs) in pancreatic neuroendocrine tumors with Ki-67 ≥10%. Patients with grade 2 tumors and with hepatic tumor load ≤25% appear to derive higher benefit from SSAs. Prospective studies are needed to validate these results to optimize tailored therapeutic strategies for this specific patient population.
长效生长抑素类似物（SSAs）是高分化晚期胃肠胰神经内分泌肿瘤（NETs）的主要一线治疗药物，但关于其在Ki-67≥10%的胰腺NETs（panNETs）中的疗效数据仍然有限。
为了评估在真实世界中，Ki-67≥10%的晚期、无功能、高分化panNETs患者接受一线长效SSAs治疗的临床结局，我们开展了一项回顾性多中心研究，纳入了2014年至2018年间在NET CONNECT网络的10个中心接受治疗的患者。主要终点是下次治疗时间（TNT）和无进展生存期（PFS），而总生存期（OS）和治疗安全性是次要终点。
共纳入73例患者（68例2级[G]，5例G3级），61例（84%）有肝转移。中位随访36.4个月（范围6 - 173个月）后，中位TNT和PFS分别为14.2个月（95%置信区间[CI]，11.6 - 16.2）和11.9个月（95%CI，8.6 - 14.1）。根据所使用的生长抑素类似物（奥曲肽与兰瑞肽）未观察到统计学显著差异，而肿瘤分级增加（风险比[HR]，4.4；95%CI，1.2 - 16.6；p = 0.04）和肝肿瘤负荷增加（HR，2；95%CI，1 - 4；p = 0.03）与PFS缩短独立相关。记录的中位OS为86个月（95%CI，56.8 - 86个月），当肝肿瘤负担>25%时观察到不良结局（HR，3.4；95%CI，1.2 - 10；p = 0.01）。14例患者报告了与治疗相关的不良事件，最常见的是腹泻。
SSAs在Ki-67≥10%的panNETs中发挥抗增殖活性，特别是在G2肿瘤中，以及肝肿瘤负荷≤25%时。
该研究结果对生长抑素类似物（SSAs）在Ki-67≥10%的胰腺神经内分泌肿瘤中的抗增殖活性提出了质疑。2级肿瘤且肝肿瘤负荷≤25%的患者似乎从SSAs中获益更高。需要进行前瞻性研究来验证这些结果，以优化针对这一特定患者群体的个体化治疗策略。
