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- Dokumenttyp:
- Article; Clinical Trial, Phase III; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
- Autor(en):
- Litton, Jennifer K; Rugo, Hope S; Ettl, Johannes; Hurvitz, Sara A; Gonçalves, Anthony; Lee, Kyung-Hun; Fehrenbacher, Louis; Yerushalmi, Rinat; Mina, Lida A; Martín, Miguel; Roché, Henri; Im, Young-Hyuck; Quek, Ruben G W; Markova, Denka; Tudor, Iulia C; Hannah, Alison L; Eiermann, Wolfgang; Blum, Joanne L
- Titel:
- Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation.
- 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 .).
- Zeitschriftentitel:
- N Engl J Med
- Jahr:
- 2018
- Band / Volume:
- 379
- Heft / Issue:
- 8
- Seitenangaben Beitrag:
- 753-763
- Volltext / DOI:
- doi:10.1056/NEJMoa1802905
- PubMed:
- http://view.ncbi.nlm.nih.gov/pubmed/30110579
- Print-ISSN:
- 0028-4793
- TUM Einrichtung:
- Frauenklinik und Poliklinik
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