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

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

doi:10.1177/17588359231186041

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

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

Affiliations

¹ Department of Clinical Oncology, A.C.Camargo Cancer Center, Sao Paulo, SP, Brazil.
² Department of Gastrointestinal Oncology, Moffit Cancer Center, Tampa, FL, USA.
³ Centro Internacional de Pesquisa, A.C.Camargo Cancer Center, Sao Paulo, SP, Brazil.
⁴ Department of Pathology, A.C.Camargo Cancer Center, Sao Paulo, SP, Brazil.
⁵ Department of Clinical Oncology A.C.Camargo Cancer Center, Rua Antônio Prudente 211, São Paulo, SP 01509-010, Brazil.

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% (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.

Keywords: clinical trial; neuroendocrine tumors; tamoxifen.

Associated data

ClinicalTrials.gov/NCT03870399