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- Titel:
Talazoparib in Patients with a Germline BRCA-Mutated Advanced Breast Cancer: Detailed Safety Analyses from the Phase III EMBRACA Trial.
- Dokumenttyp:
- Article
- Autor(en):
- Hurvitz, Sara A.; Gocalves, Anthony; Rugo, Hope S.; Lee, Yung-Hun; Fehrenbacher, Louis; Mina, Lida A.; Diab, Sami; Blum, Joanne L.; Chakrabarti, Jayeta; Elmeliegy, Mohamed; DeAnnuntis, Liza; Gauthier, Eric; Czibere, Akos; Tudor, Iulia Cristina; Quek, Ruben G. W.; Litton, Jennifer K.; Ettl, Johannes
- Abstract:
- BACKGROUND: In the EMBRACA phase III study (NCT01945775), talazoparib was associated with a significantly prolonged progression-free survival (PFS) compared with physician's choice of chemotherapy (PCT) in germline BRCA1/2-mutated HER2-negative advanced breast cancer (ABC). Herein, the safety profile of talazoparib is explored in detail. MATERIALS AND METHODS: Overall, 412 patients received ≥1 dose of talazoparib (n = 286) or PCT (n = 126). Adverse events (AEs) were evaluated, including timing, duration, and potential overlap of selected AEs. The relationship between talazoparib plasma exposure and grade ≥3 anemia was analyzed. Time-varying Cox proportional hazard models assessed the impact of dose reductions on PFS. Patient-reported outcomes (PROs) in patients with common AEs and health resource utilization (HRU) were assessed in both treatment arms. RESULTS: The most common AEs with talazoparib were hematologic (195 [68.2%] patients) and typically occurred within the first 3-4 months of receiving talazoparib. Grade 3-4 anemia lasted approximately 7 days for both arms. Overlapping grade 3-4 hematologic AEs were infrequent with talazoparib. Higher talazoparib exposure was associated with grade ≥3 anemia. Permanent discontinuation of talazoparib due to hematologic AEs was low (<2%). A total of 150 (52.4%) patients receiving talazoparib had AEs associated with dose reduction. Hematologic toxicities were managed by supportive care medication (including transfusion) and dose modifications. Among patients with anemia or nausea and/or vomiting AEs, PROs favored talazoparib. After accounting for the treatment-emergent period, talazoparib was generally associated with a lower rate of hospitalization and supportive care medication use compared with chemotherapy. CONCLUSION: Talazoparib was associated with superior efficacy, favorable PROs, and lower HRU rate versus chemotherapy in gBRCA-mutated ABC. Toxicities were manageable with talazoparib dose modification and supportive care. IMPLICATIONS FOR PRACTICE: Talazoparib was generally well tolerated in patients with germline BRCA-mutated HER2-negative advanced breast cancer in the EMBRACA trial. Common toxicities with talazoparib were primarily hematologic and infrequently resulted in permanent drug discontinuation (<2% of patients discontinued talazoparib due to hematologic toxicity). Hematologic toxicities typically occurred during the first 3-4 months of treatment and were managed by dose modifications and supportive care measures. A significant efficacy benefit, improved patient-reported outcomes, lower rate of health resource utilization and a tolerable safety profile support incorporating talazoparib into routine management of germline BRCA-mutated locally advanced/metastatic breast cancer.
- Zeitschriftentitel:
- Oncologist
- Jahr:
- 2020
- Band / Volume:
- 25
- Heft / Issue:
- 3
- Seitenangaben Beitrag:
- e439-e450
- Volltext / DOI:
- doi:10.1634/theoncologist.2019-0493
- PubMed:
- http://view.ncbi.nlm.nih.gov/pubmed/32162822
- Print-ISSN:
- 1083-7159
- TUM Einrichtung:
- Frauenklinik und Poliklinik
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