Reference Detail

Ref Type Journal Article
PMID (30110579)
Authors Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann W, Blum JL
Title Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation.
Journal The New England journal of medicine
Vol 379
Issue 8
Date 2018 08 23
URL
Abstract Text 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).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.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.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 .).

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRCA2 inact mut Her2-receptor negative breast cancer sensitive Talazoparib FDA approved Actionable In a Phase III trial (EMBRACA) that supported FDA approval, Talzenna (talazoparib) treatment resulted in significantly longer median progression-free survival (8.6 vs 5.6 months, HR=0.54, p<0.001), and higher objective response rate (62.6% vs 27.2%, OR=5.0, p<0.001) compared to standard chemotherapy in patients with advanced ERBB2 (HER2)-negative breast cancer harboring known deleterious or suspected deleterious germline mutations in BRCA1 or BRCA2 (PMID: 30110579; NCT01945775). 30110579
BRCA1 inact mut Her2-receptor negative breast cancer sensitive Talazoparib FDA approved Actionable In a Phase III trial (EMBRACA) that supported FDA approval, Talzenna (talazoparib) treatment resulted in significantly longer median progression-free survival (8.6 vs 5.6 months, HR=0.54, p<0.001), and higher objective response rate (62.6% vs 27.2%, OR=5.0, p<0.001) compared to standard chemotherapy in patients with advanced ERBB2 (HER2)-negative breast cancer harboring known deleterious or suspected deleterious germline mutations in BRCA1 or BRCA2 (PMID: 30110579; NCT01945775). 30110579