Translational Breast Cancer Research Consortium (TBCRC) 022: A Phase II Trial of Neratinib for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases
Autor: | Shannon Puhalla, Kimberly L. Blackwell, Eric P. Winer, Alarice C. Lowe, Roisin M. Connolly, Kenneth R. Hess, N. Ryabin, Nathalie Y. R. Agar, Jeffrey S. Wefel, Christina I. Herold, Nan Lin, Sarah Farooq, Polly A. Niravath, Mothaffar F. Rimawi, Elizabeth V. Lawler, Ian E. Krop, Nuhad K. Ibrahim, Rachel A. Freedman, Catherine Van Poznak, Minetta C. Liu, Beverly Moy, Michelle E. Melisko, Antonio C. Wolff, Rebecca Gelman |
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Rok vydání: | 2016 |
Předmět: |
Adult
0301 basic medicine Oncology Cancer Research medicine.medical_specialty Receptor ErbB-2 medicine.medical_treatment Breast Neoplasms Radiosurgery 03 medical and health sciences 0302 clinical medicine Breast cancer Internal medicine Clinical endpoint Humans Medicine Protein Kinase Inhibitors Human Epidermal Growth Factor Receptor 2 Objective response ERBB4 Aged Brain Neoplasms business.industry ORIGINAL REPORTS Middle Aged medicine.disease Radiation therapy 030104 developmental biology 030220 oncology & carcinogenesis Neratinib Quinolines Female business medicine.drug |
Zdroj: | Journal of Clinical Oncology. 34:945-952 |
ISSN: | 1527-7755 0732-183X |
Popis: | Purpose Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)–positive breast cancer in the CNS are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4, with promising activity in HER2-positive breast cancer; however, its activity in the CNS is unknown. We evaluated the efficacy of treatment with neratinib in patients with HER2-positive breast cancer brain metastases in a multicenter, phase II open-label trial. Patients and Methods Eligible patients were those with HER2-positive brain metastases (≥ 1 cm in longest dimension) who experienced progression in the CNS after one or more line of CNS-directed therapy, such as whole-brain radiotherapy, stereotactic radiosurgery, and/or surgical resection. Patients received neratinib 240 mg orally once per day, and tumors were assessed every two cycles. The primary endpoint was composite CNS objective response rate (ORR), requiring all of the following: ≥50% reduction in volumetric sum of target CNS lesions and no progression of non-target lesions, new lesions, escalating corticosteroids, progressive neurologic signs/symptoms, or non-CNS progression—the threshold for success was five of 40 responders. Results Forty patients were enrolled between February 2012 and June 2013; 78% of patients had previous whole-brain radiotherapy. Three women achieved a partial response (CNS objective response rate, 8%; 95% CI, 2% to 22%). The median number of cycles received was two (range, one to seven cycles), with a median progression-free survival of 1.9 months. Five women received six or more cycles. The most common grade ≥ 3 event was diarrhea (occurring in 21% of patients taking prespecified loperamide prophylaxis and 28% of those without prophylaxis). Patients in the study experienced a decreased quality of life over time. Conclusion Although neratinib had low activity and did not meet our threshold for success, 12.5% of patients received six or more cycles. Studies combining neratinib with chemotherapy in patients with CNS disease are ongoing. |
Databáze: | OpenAIRE |
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