Abstract PS12-05: First efficacy results of a 2-stage Simon’s design randomised phase 2 of darolutamide or capecitabine in patients with triple-negative, androgen receptor positive advanced breast cancer (UCBG06-3)
Authors: Bonnefoi Hervé , Lerebours Florence , Tredan Olivier , Dalenc Florence , Levy Christelle , Saghatchian Mahasti , Reynier Marie Ange Mouret , Mollon Delphine , Guiu Severine , Bouvet Laurence Venat , Carola Elisabeth , Martineau Geraldine , Pulido Marina , MacGrogan Gaetan , Goncalves Anthony 
Published: February 2021

Abstract
Background: Triple negative breast cancer (TNBC) is an heterogeneous disease and encompasses at least 4 subtypes. One of these expresses the androgen receptor (AR). Several prospective trials demonstrated antitumour efficacy with anti-androgen treatment in patients with advanced breast cancer. Darolutamide is an androgen-receptor antagonist with a potent anti-tumour efficacy in metastatic prostate cancer with a favorable safety profile. We conducted a randomized non-comparative phase II trial to study the efficacy and tolerability of darolutamide and capecitabine in AR-positive TNBC (NCT03383679).
Material and methods: Patients (Pts) with a metastatic, centrally reviewed, AR-positive (≥ 10% by immunohistochemistry) and TNBC who have received a maximum of one line of chemotherapy for advanced disease were eligible. They were randomised in a 2:1 ratio to receive darolutamide (D arm) 600 mg twice daily or capecitabine (C arm) at 1000 mg/m² twice daily 2 weeks on and 1-week off, until progression or unacceptable toxicity. The primary endpoint was clinical benefit rate (CBR) defined as the proportion of pts presenting a complete response (CR), partial response (PR), or stable disease (SD) at 16 weeks. Main secondary endpoints included objective response rate, overall survival, progression-free survival and safety. An interim statistical analysis was planned when 19 assessable pts will be available in the D arm. According to an optimal 2-stage Simon’s design,if &lt;5 patients experienced a CBR the trial should be stopped for futility; if 5 or more experienced a CBR the trial should continue up to a total of 54 patients in the D arm.
Results: Out of 133 pts screened and centrally analyzed, from 37 centres, 54% (72/133) were AR-positive. 45 pts were randomized (29 in D arm and 16 in C arm) from April 2018 to December 2019. In arm D, median age was 60 years (range 47-88). and 13.8 % received a first line of chemotherapy for metastatic disease. A total of 19 pts were eligible and assessable for the primary endpoint in D arm. 5 CBR were confirmed at 16 weeks (26.3%; 95% CI: 9.2%-51.2 %) including 1 confirmed PR and 4 SD. In arm D, fatigue (23.8%), ASAT increased (23.8%), and blood alkaline phosphatase increased (23.8%) were the most common drug-related adverse events; the majority of them being grade 1 or 2. 6 pts presented with drug-related serious adverse events: one in D arm and 5 in C arm.
Conclusions: According to the planned interim analysis, the efficacy objective is met (5 CBR) in D arm. Moreover, darolutamide is well tolerated. Thus, patients are now recruited in the second stage.
Keywords: Androgen receptor,triple-negative breast cancer, darolutamide, advanced breast cancer
Citation Format: Hervé Bonnefoi, Florence Lerebours, Olivier Tredan, Florence Dalenc, Christelle Levy, Mahasti Saghatchian, Marie Ange Mouret Reynier, Delphine Mollon, Severine Guiu, Laurence Venat Bouvet, Elisabeth Carola, Geraldine Martineau, Marina Pulido, Gaetan MacGrogan, Anthony Goncalves. First efficacy results of a 2-stage Simon’s design randomised phase 2 of darolutamide or capecitabine in patients with triple-negative, androgen receptor positive advanced breast cancer (UCBG06-3) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-05.