Abstract P3-07-25: Improved clinical outcomes on enzalutamide observed in patients with PREDICT AR+ triple-negative breast cancer: prognosis or prediction?
Authors: Miller K , Krop I , Schwartzberg L , Abramson V , Garcia-Estevez L , Eakle J , Nanda R , Yardley D , Ademuyiwa F , Chan S , Crown J , Danso M , Gelmon K , Ma L , Martinez-Janez N , Gradishar W , Steinberg J , Tudor IC , Uppal H , Paton VE , Parker J , Hudis CA , Traina TA 
Published: May 2016

Abstract
Background: A novel genomic signature that identifies androgen receptor (AR)-driven disease (PREDICT AR) is being developed for its ability to select patients (pts) who may benefit from enzalutamide (ENZA), a potent AR inhibitor.1 In a phase 2 study of triple-negative breast cancer (TNBC) pts treated with ENZA (NCT01889238) ≈ half of pts had PREDICT AR+ TNBC, with improved clinical outcomes in this sub-population.2 Because pts with hormonally driven (estrogen-receptor/progesterone-receptor[ER/PR]+) BC are thought to have a better prognosis, we investigated whether the outcomes observed in pts with PREDICT AR+ TNBC could be explained by prognosis alone.
Methods: PREDICT AR was assessed on advanced TNBC from 118 ENZA-treated pts.2 Because the duration of treatment (Tx) typically decreases with each subsequent Tx, exploratory analyses included median progression-free survival (mPFS) on ENZA vs duration of Tx prior to ENZA (used as a PFS surrogate) in pts who had received ≤1 prior Tx (data cutoff 24Mar15). Baseline characteristics by PREDICT AR status were also evaluated. An independent non-ENZA-Tx TNBC data set (after neo/adjuvant Tx)3 was probed for PREDICT AR status and clinical outcomes.
Results: ENZA-Tx pts with PREDICT AR+ TNBC (n=56; 47%) were older (66 years vs 52 years), had a longer disease-free interval (DFI) (37 vs 20 months), more bone involvement (57% vs 24%), were more likely to have had prior ER/PR+ BC (30% vs 8%), and a longer median duration on the first-line Tx (29 vs 19 weeks[wks]) vs pts with PREDICT AR- TNBC (n=62;53%).
Table 1. mPFS from ENZA-Tx pts and duration of prior Tx by PREDICT AR status and line of Tx.PREDICT AR StatusTx prior to ENZAmPFS on ENZA (wks)Median duration of prior Tx (wks)PREDICT AR+ (n=26)No prior Tx (n=10)32-- 1 prior Tx (n=16)4034PREDICT AR- (n=36)No prior Tx (n=11)8-- 1 prior Tx (n=25)1317
The prevalence of PREDICT AR+ primary TNBC from the non-ENZA-Tx dataset was 51% (n=182). DFI after neo/adjuvant therapy was not statistically different (p=0.605) between pts with PREDICT AR+ vs PREDICT AR- TNBC, and pathologic complete response rates were 23% vs 38% in PREDICT AR+ vs PREDICT AR- TNBC, respectively.
Conclusion: mPFS in pts with PREDICT AR+ TNBC who received first-line ENZA was longer than first-line Tx duration in those who received prior Tx (32 vs 29 weeks). In pts with PREDICT AR+ TNBC who received second-line ENZA, mPFS was longer than the median duration of their first-line Tx (40 vs 34 weeks). This trend was not observed in pts with PREDICT AR- TNBC. Key demographic differences did not explain these outcomes, suggesting benefit from ENZA. Duration of first-line non-ENZA-Tx was shorter in pts with PREDICT AR- TNBC vs pts with PREDICT AR+ TNBC who received second-line ENZA (17 vs 34 weeks), suggesting a better prognosis in pts with PREDICT AR+ advanced TNBC; however, PREDICT AR status was not associated with DFI following neo/adjuvant treatment for primary TNBC. PREDICT AR may identify a hormonally driven subset of pts with advanced TNBC who have a better prognosis and who may benefit from ENZA.
1. Parker J et al. J Clin Oncol 2015;33(suppl): abstr 1083.
2. Traina TA et al. J Clin Oncol 2015;33(suppl): abstr 1003.
3. Hatzis C et al. JAMA 2011;305:1873-1881.
Citation Format: Miller K, Krop I, Schwartzberg L, Abramson V, Garcia-Estevez L, Eakle J, Nanda R, Yardley D, Ademuyiwa F, Chan S, Crown J, Danso M, Gelmon K, Ma L, Martinez-Janez N, Gradishar W, Steinberg J, Tudor IC, Uppal H, Paton VE, Parker J, Hudis CA, Traina TA. Improved clinical outcomes on enzalutamide observed in patients with PREDICT AR+ triple-negative breast cancer: prognosis or prediction?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-25.