Neratinib in Combination With Trastuzumab for the Treatment of Patients With Advanced HER2-positive Breast Cancer: A Phase I/II Study.
Clin Breast Cancer
; 19(2): 97-104.e4, 2019 04.
Article
em En
| MEDLINE
| ID: mdl-30655172
ABSTRACT
BACKGROUND:
Despite the availability of several human epidermal growth factor receptor 2 (HER2)-directed treatments, many HER2-positive (HER2+) breast cancers eventually progress because of primary or acquired resistance. PATIENTS ANDMETHODS:
A 2-part, open-label, multicenter phase I/II study was conducted to determine the recommended dose of neratinib when administered with trastuzumab (part I), and to assess the antitumor activity of this combination in women with locally advanced or metastatic HER2+ breast cancer previously treated with at least 1 prior trastuzumab-based regimen (part II). Patients received oral neratinib (160 or 240 mg/d) once daily plus intravenous trastuzumab 4 mg/kg (loading dose) then 2 mg/kg weekly. Diarrhea prophylaxis was not permitted. The primary endpoint in part II was investigator-assessed 16-week progression-free survival (PFS).RESULTS:
Forty-five patients received neratinib plus trastuzumab (part I neratinib 160 mg/d, n = 4; neratinib 240 mg/d, n = 4; part II neratinib 240 mg/d, n = 37). In part I, there were no dose-limiting toxicities and the recommended neratinib dose was 240 mg/d. In part II, the 16-week PFS rate was 44.8% (90% confidence interval, 28.8%-59.6%), and the median PFS was 15.9 weeks (95% confidence interval, 15.1-31.3 weeks) in 28 evaluable patients. Three patients had durable clinical benefit lasting 9.4 to 9.7 years. Diarrhea was the most common adverse event (grade 3, n = 7 [15.6%]; grade 4, n = 0). No clinically significant cardiac toxicity was seen.CONCLUSIONS:
Neratinib in combination with trastuzumab was well-tolerated and had encouraging antitumor activity in patients with advanced trastuzumab-pretreated HER2+ breast cancer. Durable responses can be achieved in some patients.Palavras-chave
Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinolinas
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Neoplasias da Mama
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Protocolos de Quimioterapia Combinada Antineoplásica
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Receptor ErbB-2
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Inibidores de Proteínas Quinases
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Trastuzumab
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Antineoplásicos Imunológicos
Tipo de estudo:
Clinical_trials
Limite:
Adult
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Aged
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Clin Breast Cancer
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2019
Tipo de documento:
Article