Background Nearly 30% of neuroendocrine tumors (NETs) have evidence of immunohistochemical (IHC) expression of estrogen (ER) and/or progesterone (PR) receptors. Therefore, targeting ER/PR may offer an effective NET-directed treatment to select patients. Methods We conducted a multicenter Simon two-stage single-arm phase II trial of tamoxifen in patients with metastatic, progressive NETs. Eligible patients had positive IHC expression of ER and/or PR ⩾ 1%. Prior therapy with somatostatin analogs was required for progressing/functioning cases. Main exclusion criterion was aggressive disease requiring cytotoxic therapy. The primary end point was disease control rate (DCR) at week 24 by Response Evaluation Criteria in Solid Tumors version 1.1. We planned to enroll 23 patients in the first stage, to reach a DCR at week 24 of 70% (versus 50%); if ⩾12 patients reached the primary end point, a total of 37 would be included. Results From February 2019 to February 2022, 23 out of 59 patients were eligible and enrolled: 15 (65%) were females; the most common sites were pancreas (11; 48%) and small bowel (6; 26%). In all, 13 patients (56.5%) had G2 NETs. At a median follow-up of 27 months, 13 patients (56.5%) had stable disease at week 24 and median progression-free survival (PFS) was 7.9 months [interquartile range (IQR): 3.7-12.1]. The best response was stable disease in 13 patients, with most patients experiencing minor tumor growth. Median PFS times were not significantly different according to ER/PR < or ⩾30% (p = 0.49) or ER versus PR expression (p = 0.19). One patient experienced grade 2 constipation. Conclusion Tamoxifen for ER-/PR-positive NETs patients is safe but offers modest antitumor effects. Trial registry name Study of Tamoxifen in Well Differentiated Neuroendocrine Tumors and Hormone Receptor Positive Expression (HORMONET). URL https://clinicaltrials.gov/ct2/show/NCT03870399?term=03870399&draw=2&rank=1. Registration number NCT03870399.

中文翻译：

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HORMONET：他莫昔芬治疗雌激素/孕激素受体阳性神经内分泌肿瘤的 II 期试验。

背景 近 30% 的神经内分泌肿瘤 (NET) 有雌激素 (ER) 和/或孕激素 (PR) 受体的免疫组织化学 (IHC) 表达证据。因此，针对 ER/PR 可能为特定患者提供有效的 NET 导向治疗。方法 我们对转移性进展性 NET 患者进行了他莫昔芬的多中心 Simon 两阶段单臂 II 期试验。符合条件的患者的 ER 和/或 PR ≥ 1% 的 IHC 阳性表达。对于进展/功能正常的病例，需要先用生长抑素类似物进行治疗。主要排除标准是需要细胞毒治疗的侵袭性疾病。主要终点是第 24 周时的疾病控制率 (DCR)，根据实体瘤 1.1 版的反应评估标准。我们计划在第一阶段招募 23 名患者，以在第 24 周达到 70% 的 DCR（相对于 50%）；如果 12 名患者达到主要终点，则总共将包括 37 名患者。结果 2019年2月至2022年2月，59名患者中有23名符合资格并入组：15名（65%）为女性；最常见的部位是胰腺（11；48%）和小肠（6；26%）。总共有 13 名患者 (56.5%) 患有 G2 NET。在中位随访 27 个月时，13 名患者 (56.5%) 在第 24 周病情稳定，中位无进展生存期 (PFS) 为 7.9 个月 [四分位数范围 (IQR)：3.7-12.1]。13 名患者的最佳反应是疾病稳定，大多数患者经历了轻微的肿瘤生长。根据 ER/PR < 或≥30% (p = 0.49) 或 ER 与 PR 表达 (p = 0.19)，中位 PFS 时间没有显着差异。一名患者出现 2 级便秘。结论 他莫昔芬用于 ER-/PR 阳性 NET 患者是安全的，但抗肿瘤作用有限。试验注册名称他莫昔芬在高分化神经内分泌肿瘤和激素受体阳性表达中的研究（HORMONET）。网址 https://clinicaltrials.gov/ct2/show/NCT03870399?term=03870399&draw=2&rank=1。注册号 NCT03870399。