Abstract P6-18-12: EMBRACA: Efficacy and safety of talazoparib or physician's choice of therapy in patients with advanced breast cancer and a germline BRCA1/2 mutation: A regional analysis
Authors: Mina L , Lee K-H , Gonçalves A , Woodward N , Hurvitz SA , Diab S , Yerushalmi R , Goodwin A , Moreira Costa Zorzetto M , Kim S-B , Czibere A , Tudor IC , Gauthier E , Litton JK , Ettl J 
Published: May 2019

Background: Talazoparib (TAL) prevents DNA damage repair by inhibiting poly (ADP-ribose) polymerase (PARP) enzymes and trapping PARP on DNA, resulting in cell death in BRCA1/2-mutated cells.

Methods: EMBRACA is an open-label, randomized, 2-arm phase 3 trial in which efficacy and safety of TAL (1 mg/d) were compared with physician's choice of therapy (PCT; capecitabine, eribulin, gemcitabine, vinorelbine) in patients (pts) with locally advanced or metastatic breast cancer (ABC) and a germline BRCA mutation (gBRCAm). Outcomes were assessed by region of the world (North America [NA]; Europe [EU]; rest of world [ROW]). Progression-free survival (PFS), objective response rate (ORR), and clinical benefit rate (CBR) at 24 wks were assessed; safety was also assessed.

Results: 431 pts were randomized 2:1. Pt characteristics were well balanced, although a higher percentage of pts in ROW had more severe disease (eg, triple-negative breast cancer [TNBC], Disease-free interval [DFI]&lt;12 mo, more distant metastases, more disease sites) and were on average younger than pts in NA/EU. TAL provided improvement in PFS, ORR, and CBR in all regions vs PCT. The most common toxicities with TAL included anemia, neutropenia, thrombocytopenia, fatigue, and nausea for all regions. Alopecia was less frequent with TAL in EU/ROW. Serious adverse events for pts receiving TAL were more frequent in EU than NA/ROW. Incidences of adverse events associated with permanent treatment discontinuation in pts receiving TAL were low in all regions and generally lower than for PCT.

Table 1CategoryNA* (N=156)EU* (N=190)ROW* (N=85)Mean age, years49.049.244.2Race, %   White76.971.152.9Black5.8-3.5Asian5.8-42.4Not reported-27.4-TNBC, %424447BRCA1**, %414748BRCA2**, %595352DFI&lt;12 mo, %313444Distant metastases, %949397≥3 disease sites, %474049PFS, (hazard ratio [HR]; [95% CI]); P value0.46 [0.29-0.74] P=.00090.52 [0.33-0.80]; P&lt;.0030.57 [0.31-1.07] ;P=.08ORR (odds ratio [OR] [95% CI]); P value5.54 [2.4-16.1];P&lt;.00013.75 [1.57-9.87]; P=.0016.7 [1.61-28.39]; P=.001CBR (OR [95% CI]); P value4.71 [2.20-10.57]; P&lt;.00013.39 [1.56-7.36]; P=.00075.70 [1.70-17.13]; P=.002Hematologic AEs, %   Anemia50.558.642.6Neutropenia31.332.346.3Thrombocytopenia28.322.635.2Nonhematologic AEs, %   Fatigue59.643.650.0Nausea47.545.957.4Headache32.330.837.0Alopecia34.320.320.4Serious adverse events, %25.340.622.2Treatment discontinuation, n/N, (%)   TAL7/99 (7.1)12/133 (9.0)3/54 (5.6)PCT7/43 (16.3)3/54 (5.6)2/29 (6.9)AE, adverse event; CI, confidence interval; *NA (United States); EU (Belgium, France, Germany, Ireland, Italy, Poland, Spain, United Kingdom, Russia, Ukraine, Israel); ROW (Brazil, Korea, Australia, Taiwan).**Central laboratory.

Conclusions: In pts with gBRCAm ABC, TAL demonstrated significant improvements in clinical outcomes compared with PCT regardless of the region of the world in which they lived. However, slight differences among the regions in baseline characteristics were noted, possibly due to regional variation in diagnosis and detection of gBRCAm ABC as well as different treatment paradigms for metastatic breast cancer.

Funding: Medivation LLC, acquired by Pfizer.

Citation Format: Mina L, Lee K-H, Gonçalves A, Woodward N, Hurvitz SA, Diab S, Yerushalmi R, Goodwin A, Moreira Costa Zorzetto M, Kim S-B, Czibere A, Tudor IC, Gauthier E, Litton JK, Ettl J. EMBRACA: Efficacy and safety of talazoparib or physician's choice of therapy in patients with advanced breast cancer and a germline BRCA1/2 mutation: A regional analysis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-12.