Phase II neoadjuvant clinical trial of carboplatin and eribulin in women with triple negative early-stage breast cancer (NCT01372579)
| Autor: | Krystal Brown, Sara Barnato Giordano, Kent Hoskins, Kirsten Timms, Cara Solimeno, Seema A. Khan, Kevin P. Bethke, William J. Gradishar, Alexander Gutin, Vamsi Parini, Irene Helenowski, Joshua Jones, Jacqueline S. Jeruss, Anne Renee Hartman, Steven T. Rosen, Borko Jovanovic, Victor Abkevich, Kalliopi P. Siziopikou, Regina Uthe, Virginia G. Kaklamani, Elisha Hughes, Sarika Jain, Jamie H. Von Roenn, Nora M. Hansen, Caitlin Meservey, Zaina Sangale |
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| Rok vydání: | 2015 |
| Předmět: |
Oncology
Adult Cancer Research medicine.medical_specialty Cyclin E Cyclin D medicine.medical_treatment Genes BRCA2 Genes BRCA1 Triple Negative Breast Neoplasms Kaplan-Meier Estimate Carboplatin chemistry.chemical_compound Breast cancer Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Clinical endpoint Odds Ratio Humans Furans Neoadjuvant therapy Triple-negative breast cancer Aged Neoplasm Staging Gynecology biology business.industry Ketones Middle Aged medicine.disease Neoadjuvant Therapy Treatment Outcome chemistry Mutation biology.protein Female Neoplasm Grading business Biomarkers Eribulin |
| Zdroj: | Breast cancer research and treatment. 151(3) |
| ISSN: | 1573-7217 |
| Popis: | The purpose of this study is to evaluate the efficacy and safety of neoadjuvant treatment with carboplatin and eribulin in patients with early-stage triple negative breast cancer (TNBC), and to explore biomarkers based on DNA and protein expression profiles as predictors of response. Patients with histologically confirmed early-stage TNBC received carboplatin AUC 6 iv every 21 days, and eribulin 1.4 mg/m(2) day 1 and day 8 every 21 days for four cycles. The primary endpoint of the study was pathologic complete response (pCR), with secondary endpoints including clinical response and safety of the combination. Exploratory studies assessed DNA-based biomarkers [homologous recombination deficiency (HRD) score, and HR deficiency status (HRD score + BRCA1/BRCA2 mutation status)], protein-based biomarkers (Ki67, TP53, androgen receptor, Cyclin E, CDK2, Cyclin D, CDK4, Pin1 and Smad3), and clinical pretreatment factors as predictors of pCR. 13/30 (43.3 %) patients enrolled in the study achieved pCR. 24 (80.0 %) had a clinical complete or partial response. The combination was safe with mostly grade 1 and 2 toxicities. HRD score (P = 0.0024) and HR deficiency status (P = 0.0012) significantly predicted pCR. Pretreatment cytoplasmic CDK2 was also associated with pCR (P = 0.021). Significant differences in pre- versus post-treatment expression levels of nuclear Cyclin D (P = 0.020), nuclear CDK4 (P = 0.0030), and nuclear Smad3 (P = 0.015) were detected. The combination of carboplatin and eribulin is safe and efficacious in the treatment of early-stage TNBC. HRD score, HR deficiency status, and cytoplasmic CDK2 predicted pCR in this patient population. |
| Databáze: | OpenAIRE |
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