J. Litton, H. Rugo, J. Ettl
Feb 15, 2018
Citations
2
Influential Citations
57
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Quality indicators
Journal
Cancer Research
Abstract
Background: Talazoparib (TALA) is a highly potent, dual-mechanism PARP inhibitor that inhibits the PARP enzyme and effectively traps PARP on single-stranded DNA breaks, preventing DNA damage repair and causing cell death in BRCA1/2-mutated cells. Methods: EMBRACA is an open-label, randomized, 2-arm, phase 3 trial comparing the efficacy and safety of TALA (1 mg/day) with standard single-agent physician9s choice of therapy (PCT) (capecitabine, eribulin, gemcitabine, or vinorelbine) in patients with advanced breast cancer (aBC) and a germline BRCA1/2 mutation (gBRCAmut). The primary objective was PFS assessed by blinded independent central review (BICR). Secondary objectives: OS, ORR, CBR at 24 weeks (CBR24), and safety. Exploratory objectives: patient-reported QoL and DOR. Eligibility criteria: age ≥ 18 years; HER2-negative aBC; deleterious or suspected deleterious gBRCAmut; ≤ 3 prior cytotoxic regimens for aBC; and ECOG PS ≤ 2. Prior platinum was allowed. Patients were randomized 2:1 and stratified by receptor status, extent of prior therapy, and CNS metastases (NCT01945775). Results: 431 patients were randomized (median age 46 years; 54% hormone-receptor [HR]+ BC; 45% BRCA1+ and 55% BRCA2+; 55% ECOG PS = 0; 38% chemo-naive for aBC; 18% prior platinum; 15% CNS metastases); 287 were assigned to TALA and 144 to PCT (1 TALA, 18 PCT patients were not treated). Median duration of exposure was 6.1 and 3.9 months, respectively; TALA had a relative dose intensity of 87%. At 62% PFS data maturity: Improved clinical benefit was seen in all subsets including those with HR+ BC (HR 0.47; 95% CI 0.32-0.71) and CNS metastasis (HR 0.32; 95% CI 0.15-0.88). There was a significant delay in the time to deterioration in global health status (GHS)/QoL for TALA vs PCT (HR 0.38; 95% CI 0.26-0.55; P Citation Format: Litton J, Rugo HS, Ettl J, Hurvitz S, Goncalves A, Lee K-H, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roche H, Im Y-H, Quek RGW, Tudor IC, Hannah AL, Eiermann W, Blum JL. EMBRACA: A phase 3 trial comparing talazoparib, an oral PARP inhibitor, to physician9s choice of therapy in patients with advanced breast cancer and a germline BRCA mutation [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 GS6-07.