Randomized Phase II Trial of Everolimus in Combination With Tamoxifen in Patients With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer With Prior Exposure to Aromatase Inhibitors: A GINECO Study
Autor: | Sophie Abadie-Lacourtoisie, Claire Cropet, Jean-Marc Ferrero, Thomas Bachelot, Jean-Christophe Eymard, Isabelle Ray-Coquard, Eric Pujade-Lauraine, Gilles Freyer, Marc Debled, Céline Bourgier, Dominique Spaeth, D. Allouache, Eric Legouffe, Claude El Kouri |
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Rok vydání: | 2012 |
Předmět: |
Adult
Oncology Cancer Research medicine.medical_specialty Receptor ErbB-2 Phases of clinical research Breast Neoplasms Pharmacology Internal medicine Antineoplastic Combined Chemotherapy Protocols Humans Medicine Everolimus Neoplasm Metastasis Aromatase skin and connective tissue diseases Aged Aged 80 and over Sirolimus biology Aromatase Inhibitors business.industry Middle Aged medicine.disease Metastatic breast cancer Tamoxifen Receptors Estrogen Hormone receptor biology.protein Female Receptors Progesterone business medicine.drug Hormone |
Zdroj: | Journal of Clinical Oncology. 30:2718-2724 |
ISSN: | 1527-7755 0732-183X |
Popis: | Purpose Cross-talk between signal transduction pathways likely contributes to hormone resistance in metastatic breast cancer (mBC). Everolimus, an oral inhibitor of the mammalian target of rapamycin, has restored sensitivity in endocrine-resistance models and shown anticancer activity in early-phase mBC clinical trials. This analysis evaluated efficacy and safety of everolimus in combination with tamoxifen in patients with mBC resistant to aromatase inhibitors (AIs). Patients and Methods This open-label, phase II study randomly assigned postmenopausal women with hormone receptor–positive, human epidermal growth factor receptor 2–negative, AI-resistant mBC to tamoxifen 20 mg/d plus everolimus 10 mg/d (n = 54) or tamoxifen 20 mg/d alone (n = 57). Randomization was stratified by primary and secondary hormone resistance. Primary end point was clinical benefit rate (CBR), defined as the percentage of all patients with a complete or partial response or stable disease at 6 months. No formal statistical comparison between groups was planned. Results The 6-month CBR was 61% (95% CI, 47 to 74) with tamoxifen plus everolimus and 42% (95% CI, 29 to 56) with tamoxifen alone. Time to progression (TTP) increased from 4.5 months with tamoxifen alone to 8.6 months with tamoxifen plus everolimus, corresponding to a 46% reduction in risk of progression with the combination (hazard ratio [HR], 0.54; 95% CI, 0.36 to 0.81). Risk of death was reduced by 55% with tamoxifen plus everolimus versus tamoxifen alone (HR, 0.45; 95% CI, 0.24 to 0.81). The main toxicities associated with tamoxifen plus everolimus were fatigue (72% v 53% with tamoxifen alone), stomatitis (56% v 7%), rash (44% v 7%), anorexia (43% v 18%), and diarrhea (39% v 11%). Conclusion This study suggests that tamoxifen plus everolimus increased CBR, TTP, and overall survival compared with tamoxifen alone in postmenopausal women with AI-resistant mBC. |
Databáze: | OpenAIRE |
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