Neoadjuvant Talazoparib for Patients With Operable Breast Cancer With a Germline BRCA Pathogenic Variant
| Autor: | Abenaa M. Brewster, Rashmi Krishna Murthy, Alastair M. Thompson, Nuhad K. Ibrahim, Vicente Valero, Sarah M. DeSnyder, Senthil Damodaran, Helen Piwnica-Worms, Stacy L. Moulder, Gary J. Whitman, Thorunn Helgason, Jennifer K. Litton, Beatriz E. Adrada, Jill Schwartz-Gomez, Kenneth R. Hess, Carlos H. Barcenas, Banu Arun, Elizabeth A. Mittendorf, Marion E. Scoggins |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
0301 basic medicine Oncology Cancer Research medicine.medical_specialty medicine.medical_treatment Administration Oral Breast Neoplasms Pilot Projects Triple Negative Breast Neoplasms Poly(ADP-ribose) Polymerase Inhibitors Germline Medication Adherence 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Germline mutation Breast cancer Internal medicine RAPID COMMUNICATIONS Humans Medicine Talazoparib Germ-Line Mutation Neoadjuvant therapy BRCA2 Protein Chemotherapy BRCA1 Protein business.industry Middle Aged medicine.disease Metastatic breast cancer Neoadjuvant Therapy Clinical trial 030104 developmental biology chemistry Chemotherapy Adjuvant 030220 oncology & carcinogenesis Phthalazines Female business |
| Zdroj: | J Clin Oncol |
| ISSN: | 1527-7755 0732-183X |
| Popis: | PURPOSE Talazoparib has demonstrated efficacy in patients with BRCA-positive metastatic breast cancer. This study evaluated the pathologic response of talazoparib alone for 6 months in patients with a known germline BRCA pathogenic variant (g BRCA-positive) and operable breast cancer. METHODS Eligibility included 1 cm or larger invasive tumor and g BRCA-positive disease. Human epidermal growth factor receptor 2–positive tumors were excluded. Twenty patients underwent a pretreatment biopsy, 6 months of once per day oral talazoparib (1 mg), followed by definitive surgery. Patients received adjuvant therapy at physician’s discretion. The primary end point was residual cancer burden (RCB). With 20 patients, the RCB-0 plus RCB-I response rate can be estimated with a 95% CI with half width less than 20%. RESULTS Twenty patients were enrolled from August 2016 to September 2017. Median age was 38 years (range, 23 to 58 years); 16 patients were g BRCA1 positive and 4 patients were g BRCA2 positive. Fifteen patients had triple-negative breast cancer (estrogen receptor/progesterone receptor < 10%), and five had hormone receptor-positive disease. Five patients had clinical stage I disease, 12 had stage II, and three had stage III, including one patient with inflammatory breast carcinoma and one with metaplastic chondrosarcomatous carcinoma. One patient chose to receive chemotherapy before surgery and was not included in RCB analyses. RCB-0 (pathologic complete response) rate was 53% and RCB-0/I was 63%. Eight patients (40%) had grade 3 anemia and required a transfusion, three patients had grade 3 neutropenia, and 1 patient had grade 4 thrombocytopenia. Common grade 1 or 2 toxicities were nausea, fatigue, neutropenia, alopecia, dizziness, and dyspnea. Toxicities were managed by dose reduction and transfusions. Nine patients required dose reduction. CONCLUSION Neoadjuvant single-agent oral talazoparib once per day for 6 months without chemotherapy produced substantial RCB-0 rate with manageable toxicity. The substantive pathologic response to single-agent talazoparib supports the larger, ongoing neoadjuvant trial (ClinicalTrials.gov identifier: NCT03499353 ). |
| Databáze: | OpenAIRE |
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