Abstract P5-23-04: Men with advanced breast cancer (BC): Initial phase (Ph) 2 clinical activity of seviteronel, a selective CYP17-lyase and androgen receptor (AR) inhibitor
Authors: Elias A , Gucalp A , Bardia A , Resaul A , Eisner J , Baskin-Bey E , Traina TA 
Published: February 2018

Abstract
Background:
Seviteronel (Sevi), an oral selective CYP17-lyase and AR inhibitor that blocks testosterone and estradiol production whilst competitively antagonizing the AR, is in Ph 2 clinical development for the treatment of advanced prostate and breast cancers (BC). Male BC is a high unmet need. Men with BC have a high rate of advanced disease at the time of diagnosis and disease-related deaths but no approved therapies. A majority of male BC tumors are AR+ (≥85%; Sas-Korczynska et al. Pol J Pathol. 2015; 66:347-52) suggesting a role for AR-directed therapies. The primary objective of this ongoing Ph 2 study (NCT02580448) is to estimate the activity of once daily Sevi in men with BC as measured by clinical benefit rate (CBR; proportion of pts with stable disease/partial response/complete response) at 16 weeks (wks).
Methods:
Male patients (pts) with ER+/HER2-normal locally advanced or metastatic BC following progression of at least 1 prior line of endocrine therapy were enrolled. Pts were ECOG 0 or 1 and undergoing gonadal suppression at the time of study entry. Evaluable (Eval) pts received at least 1 dose of Sevi, had 1 post-baseline scan, and were either discontinued or were on study at wk 16. Sevi was administered at 600 mg oral daily. Scans were performed every 8 wks. A Simon's 2-stage design was employed to determine activity (≥1 of 7 Eval pts with CBR16 allowed for accrual to Stage 2; total Ph 2 enrollment target of 18 Eval pts).
Results:
As of 01 June 2017, 7 men with BC were enrolled. Median age was 58y [53, 70] (median [range]) and 71% were ECOG = 1. 71% had visceral metastases; 14% with brain, 43% with liver and 57% with lung involvement. Median lines of prior therapies for BC in any setting was 9 [5, 22]. All pts enrolled had at least one line of prior therapy for advanced disease and 71% had ≥2 prior lines; these included hormonal therapy (14%), chemotherapy (14%) and hormonal + chemotherapy (43%). Median Sevi treatment duration was 58d [41, 185] and one pt is ongoing. One pt met CBR16, allowing for accrual to Stage 2. All discontinuations were for disease progression (n=6). The most common adverse events (≥2 pts) were fatigue (71%), back pain (29%), constipation (29%), decreased appetite (29%), dizziness (29%), hot flushes (29%), insomnia (29%) and nausea (29%); all Grade 1/2 except for one case of Grade 3 nausea. Updated duration of treatment and CBR data will be presented at the time of presentation.
Conclusions:
Seviteronel is active in male BC and was well tolerated with no discontinuations due to AEs. Stage 1 criteria for Sevi activity was met and full Ph 2 enrollment is ongoing for men with BC. In comparison to women with ER+ BC treated with Sevi in Ph 2 (Gucalp et al, ASCO 2017), men had more advanced disease (e.g., visceral disease and prior treatments for metastatic disease). Sevi may provide a novel treatment option for ER+ BC in heavily pre-treated men with high disease burden.
Citation Format: Elias A, Gucalp A, Bardia A, Resaul A, Eisner J, Baskin-Bey E, Traina TA. Men with advanced breast cancer (BC): Initial phase (Ph) 2 clinical activity of seviteronel, a selective CYP17-lyase and androgen receptor (AR) inhibitor [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-23-04.