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. 2022 Feb 10;2(1):9-18.
doi: 10.1530/EO-21-0009. eCollection 2022 Jan.

SAKK 21/12: a phase II trial of transdermal CR1447 in breast cancer patients

Marcus Vetter  1   2 , Karin M Rothgiesser  3 , Qiyu Li  3 , Hanne Hawle  3 , Wolfgang Schönfeld  4 , Karin Ribi  3   5 , Salome Riniker  6 , Roger von Moos  7 , Andreas Trojan  8 , Elena Kralidis  9 , Mathias Fehr  10 , Andreas Müller  11 , Beat Thürlimann  6 ; Swiss Group for Clinical Cancer Research (SAKK)
Affiliations

SAKK 21/12: a phase II trial of transdermal CR1447 in breast cancer patients

Marcus Vetter et al. Endocr Oncol. .

Abstract

Objective: CR1447, a novel transdermal formulation of 4-hydroxytestosterone, has aromatase-inhibiting and androgen receptor (AR)-modulating properties (IC504.4 nM) with antitumor effects against AR-positive tumor cells in vitro. This trial investigated the efficacy and safety of CR1447 for patients with metastatic estrogen receptor-positive (A) and AR-positive triple-negative breast cancers (B).

Design and methods: (A) included patients with at most one prior endocrine therapy line without progression ≥6 months, whereas (B) included patients with ≤2 prior chemotherapy lines, all displaying advanced signs of disease. The primary endpoint was disease control at week 24 (DC24). The null hypothesis was DC24 ≤30% (A) and ≤15% (B). Thirty-seven patients were recruited (29 in (A) and 8 in (B)); accrual was stopped following an interim analysis demonstrating futility in (A) and slow accrual in (B).

Results: DC24 was attained in 5/21 (95% CI: 8.2-47.2) patients in (A) and none in (B). The median progression-free survival was 5.1 months (95% CI: 2.5-5.6) in (A) and 2.5 months (95% CI: 0.7-2.6) in (B). The median overall survival was 24.6 months (95% CI: 22.9-not applicable) in (A) and 10.8 months (95% CI: 3.3-10.9) in (B). CR1447 had a favorable safety profile without treatment-related grade 3-5 toxicities in (A). Especially no side effects linked to androgenic effects were observed.

Conclusions: Despite this trial being negative, the 24% DC24 rate in a second-line setting, and the prolonged partial response experienced by a patient, indicate activity. Further evaluation of CR1447 in endocrine-sensitive patients or combination trials appears warranted.

Keywords: CR1447; androgen receptor; endocrine therapy; estrogen receptor; metastatic breast cancer.

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Conflict of interest statement

W S is a scientific advisor for CURADIS. The other authors have nothing to disclose.

Figures

Figure 1
Figure 1
Prior endocrine therapy cohort. Patients who reached DC24 had longer previous endocrine therapy than patients without DC24.
Figure 2
Figure 2
Outcome of patients in cohort A and B. PFS and OS probability. A_E, stratum A eligible patients; A_NE, stratum A not eligible patients; OS, overall survival; PFS, progression-free survival.
See this image and copyright information in PMC

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