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N Engl J Med. 2018 Aug 23;379(8):753-763. doi: 10.1056/NEJMoa1802905. Epub 2018 Aug 15.

Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation.

Author information

1
From the University of Texas M.D. Anderson Cancer Center, Houston (J.K.L.), and the Texas Oncology-Baylor Charles A. Sammons Cancer Center, US Oncology Network, Dallas (J.L.B.) - both in Texas; University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center (H.S.R.), and Pfizer (R.G.W.Q., D.M., I.C.T., A.L.H.), San Francisco, University of California, Los Angeles, Los Angeles (S.A.H.), and Kaiser Permanente, Northern California, Vallejo (L.F.) - all in California; the Department of Obstetrics and Gynecology, Klinikum Rechts der Isar, Technische Universität München (J.E.), and Interdisziplinäres Onkologisches Zentrum München (W.E.) - both in Munich, Germany; Institut Paoli-Calmettes, Marseille (A.G.), and Institut Claudius Regaud, Institut Universitaire du Cancer Toulouse, Toulouse (H.R.) - both in France; Seoul National University Hospital (K.-H.L.) and Samsung Medical Center (Y.-H.I.) - both in Seoul, South Korea; Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel (R.Y.); Banner M.D. Anderson Cancer Center, Gilbert, AZ (L.A.M.); and Instituto de Investigación Sanitaria Gregorio Marañón, Centro de Investigación Biomédica en Red Oncología, Grupo Español de Investigación en Cáncer de Mama, Universidad Complutense, Madrid (M.M.).

Abstract

BACKGROUND:

The poly(adenosine diphosphate-ribose) inhibitor talazoparib has shown antitumor activity in patients with advanced breast cancer and germline mutations in BRCA1 and BRCA2 ( BRCA1/2).

METHODS:

We conducted a randomized, open-label, phase 3 trial in which patients with advanced breast cancer and a germline BRCA1/2 mutation were assigned, in a 2:1 ratio, to receive talazoparib (1 mg once daily) or standard single-agent therapy of the physician's choice (capecitabine, eribulin, gemcitabine, or vinorelbine in continuous 21-day cycles). The primary end point was progression-free survival, which was assessed by blinded independent central review.

RESULTS:

Of the 431 patients who underwent randomization, 287 were assigned to receive talazoparib and 144 were assigned to receive standard therapy. Median progression-free survival was significantly longer in the talazoparib group than in the standard-therapy group (8.6 months vs. 5.6 months; hazard ratio for disease progression or death, 0.54; 95% confidence interval [CI], 0.41 to 0.71; P<0.001). The interim median hazard ratio for death was 0.76 (95% CI, 0.55 to 1.06; P=0.11 [57% of projected events]). The objective response rate was higher in the talazoparib group than in the standard-therapy group (62.6% vs. 27.2%; odds ratio, 5.0; 95% CI, 2.9 to 8.8; P<0.001). Hematologic grade 3-4 adverse events (primarily anemia) occurred in 55% of the patients who received talazoparib and in 38% of the patients who received standard therapy; nonhematologic grade 3 adverse events occurred in 32% and 38% of the patients, respectively. Patient-reported outcomes favored talazoparib; significant overall improvements and significant delays in the time to clinically meaningful deterioration according to both the global health status-quality-of-life and breast symptoms scales were observed.

CONCLUSIONS:

Among patients with advanced breast cancer and a germline BRCA1/2 mutation, single-agent talazoparib provided a significant benefit over standard chemotherapy with respect to progression-free survival. Patient-reported outcomes were superior with talazoparib. (Funded by Medivation [Pfizer]; EMBRACA ClinicalTrials.gov number, NCT01945775 .).

PMID:
30110579
DOI:
10.1056/NEJMoa1802905
[Indexed for MEDLINE]

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