Bosutinib in Combination With the Aromatase Inhibitor Exemestane: A Phase II Trial in Postmenopausal Women With Previously Treated Locally Advanced or Metastatic Hormone Receptor-Positive/HER2-Negative Breast Cancer
| Autor: | Charles Zacharchuk, Ladan Duvillie, Meritxell Bellet, Kathleen Turnbull, Tomasz Sarosiek, Beverly Moy, István Láng, Patrick Neven, Fabienne Lebrun, Nathalie Bardy-Bouxin, Eric Leip, Louis W.C. Chow, Paul E. Goss, Binghe Xu |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
medicine.drug_class Receptor ErbB-2 Locally advanced Antineoplastic Agents Breast Neoplasms Disease-Free Survival chemistry.chemical_compound Breast cancer Exemestane Antineoplastic Combined Chemotherapy Protocols Nitriles medicine Humans Protein Kinase Inhibitors Aromatase inhibitor Aniline Compounds business.industry Aromatase Inhibitors Clinical Trial Results medicine.disease Androstadienes Postmenopause Oncology chemistry Receptors Estrogen Hormone receptor Cancer research Quinolines Female business Receptors Progesterone Bosutinib Proto-oncogene tyrosine-protein kinase Src medicine.drug Hormone |
| Popis: | Author Summary Background. Bosutinib is an oral, selective Src/Abl tyrosine kinase inhibitor with activity in breast cancer (BC). We evaluated bosutinib plus exemestane as second-line therapy in previously treated hormone receptor-positive (HR+) locally advanced or metastatic BC. Methods. This was a phase II study with patients enrolled in a single-arm safety lead-in phase. Patients receiving bosutinib at 400 mg or 300 mg/day (based on toxicity) plus exemestane at 25 mg/day were monitored for adverse events (AEs) and dose-limiting toxicities for 28 days, and initial efficacy was assessed. After the lead-in and dose-determination phase, randomized evaluation of combination therapy versus exemestane was planned. Results. Thirty-nine of 42 patients (93%) experienced treatment-related AEs including diarrhea in 28 (67%) and hepatotoxicity in 11 (26%); overall serious treatment-related AEs were recorded in 4 (10%). No liver toxicity met Hy's law criteria. Dose-limiting toxicities occurred in 5 of 13 patients receiving 400 mg (38%) and 3 of 26 patients receiving 300 mg (12%) of bosutinib; all resolved on treatment discontinuation. One patient (300 mg/day) achieved confirmed partial response; three (400 mg/day, n = 2; 300 mg/day, n = 1) maintained stable disease for >24 weeks; a best response of progressive disease occurred in 15 of 42 patients (36%). Median progression-free survival was 12.3 weeks (80% confidence interval: 11.0–15.6). Conclusion. The risk-benefit profile of bosutinib at 300 mg/day plus exemestane resulted in early study termination before the randomized portion. Alternative bosutinib regimens merit investigation in BC. |
| Databáze: | OpenAIRE |
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