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。

HORMONET: a phase II trial of tamoxifen for estrogen/progesterone receptor-positive neuroendocrine tumors.

作者信息

Barros Milton J, Strosberg Jonathan, Al-Toubah Taymeyah, de Jesus Victor Hugo F, Durant Lais, Mello Celso A, Felismino Tiago C, De Brot Louise, Taboada Rodrigo G, Donadio Mauro D, Riechelmann Rachel P

机构信息

Department of Clinical Oncology, A.C.Camargo Cancer Center, Sao Paulo, SP, Brazil.

Department of Gastrointestinal Oncology, Moffit Cancer Center, Tampa, FL, USA.

出版信息

Ther Adv Med Oncol. 2023 Jul 29;15:17588359231186041. doi: 10.1177/17588359231186041. eCollection 2023.

DOI:10.1177/17588359231186041

PMID:37529158

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10387775/

Abstract

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% ( 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% ( = 0.49) or ER PR expression ( = 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.

摘要

背景

近30%的神经内分泌肿瘤（NETs）有雌激素（ER）和/或孕激素（PR）受体免疫组化（IHC）表达的证据。因此，针对ER/PR可能为部分患者提供有效的NET靶向治疗。

方法

我们对转移性、进展性NETs患者进行了一项他莫昔芬的多中心西蒙两阶段单臂II期试验。符合条件的患者ER和/或PR的IHC表达阳性且≥1%。进展期/功能性病例需要先前接受生长抑素类似物治疗。主要排除标准是需要细胞毒性治疗的侵袭性疾病。主要终点是根据实体瘤疗效评价标准1.1版在第24周时的疾病控制率（DCR）。我们计划在第一阶段纳入23例患者，使第24周时的DCR达到70%（50%）；如果≥12例患者达到主要终点，则总共纳入37例。

结果

从2019年2月至2022年2月，59例患者中有23例符合条件并被纳入：15例（65%）为女性；最常见的部位是胰腺（11例；48%）和小肠（6例；26%）。总共13例患者（56.5%）患有G2级NETs。中位随访27个月时，13例患者（56.5%）在第24周时疾病稳定，中位无进展生存期（PFS）为7.9个月[四分位间距（IQR）：3.7 - 12.1]。最佳反应是13例患者疾病稳定，大多数患者肿瘤有轻微生长。根据ER/PR <或≥30%（P = 0.49）或ER PR表达（P = 0.19），中位PFS时间无显著差异。1例患者出现2级便秘。