Abstract 897P
Background
Nearly 20% of NET have positive immunohistochemical (IHC) expression of ER and/or PR. Targeting ER/PR may benefit selected NET pts.
Methods
Multicenter Simon two-stage single-arm phase II trial of tamoxifen 20mg PO daily until progression (PD). Eligible pts had progressive metastatic NET and positive IHC expression of ER and/or PR ≧ 1%. Prior somatostatin analogues (SSA) were required and kept in functioning NET. Main exclusion criteria: aggressive NET requiring cytotoxic therapy, oral anticoagulants, thromboembolism in the last 12 months. Imaging was performed every 12 weeks. Primary endpoint was disease control (DCR) at week 24 by RECIST 1.1. H0 was DCR at week 24 of 50%; H1 was DCR of 70%. Considering a dropout rate of 30%, alpha and beta errors of 5% and 20%, we planned to enroll 23 in the first stage; if ≥ 12 pts reached the primary endpoint, a total of 37 pts would be enrolled. If 23 out of 37 reached DCR at week 24, the trial would be positive.
Results
From Feb 2019 to Feb 2022, 88 pts were screened, 23 were eligible and enrolled: median age was 56, 15 (65%) were female, the most common sites were pancreas (11; 47.8%) and small bowel (5; 21.7%), 17 (74%) had nonfunctioning NET, 8 (34.8%), 13 (56.5%) and 2(8.7%) had G1, G2, G3 NET, respectively. At a median follow up of 27 months, 19 pts had PD, 1 died from postoperative complications at week 6, one is on trial, 2 stopped treatment at weeks 24 and 108 without PD. Twelve pts (52%) had DCR at week 24. Median progression-free survival (PFS) was 8 months (interquartile range [IQR]: 3.7 to 12.1). Best response was stable disease in 11 pts and 8 had PD at week 12. Median PFS was 6.1 months (IQR: 3.5 – 8.4) vs 9.4 months (IQR: 3.9 – 14.6), according to ER/PR < or ≥ 30% (logrank p = 0.48). The table describes pts with ER/PR ≥ 30% NET and week of PD. There were no grade ≥ 3 adverse events. Table: 897P
Pts with ER/PR ≥ 30% NET
| ER/PR % | Grade | Ki67 % | Primary site | Week of PD |
| 30/0 | 3 | 40 | Lung | 24 |
| 50/0 | 2 | 6 | Small bowel | 36 |
| 0/70 | 2 | 15 | Pancreas | 60 |
| 10/90 | 2 | 10 | Pancreas | 48 |
| 0/80 | 2 | 10 | Pancreas | 12 |
| 40/0 | 1 | 1 | Small bowel | 95 |
| 30/60 | 2 | 10 | Ampulla | 12 |
Conclusions
Tamoxifen for ER/PR-positive NET pts is safe but offers modest antitumor effects.
Clinical trial identification
NCT03870399.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
AC Camargo Cancer Center.
Disclosure
R.S.P. Riechelmann: Financial Interests, Personal, Invited Speaker: Novartis. J. Strosberg: Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Royalties: uptodate; Financial Interests, Institutional, Invited Speaker: Novartis, Merck. M.D. Spina Donadio: Financial Interests, Personal, Invited Speaker: Novartis. All other authors have declared no conflicts of interest.