Neratinib in Combination With Trastuzumab for the Treatment of Patients With Advanced HER2-positive Breast Cancer: A Phase I/II Study
| Autor: | Daniel Hunt, Shukui Qin, Lori J. Goldstein, K. Tkaczuk, Kimberly L. Blackwell, Mario Campone, Khalil Zaman, Richard Bryce |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology Adult Cancer Research medicine.medical_specialty Receptor ErbB-2 Breast Neoplasms Loading dose 03 medical and health sciences Young Adult 0302 clinical medicine Breast cancer Antineoplastic Agents Immunological Trastuzumab Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Clinical endpoint Humans skin and connective tissue diseases Adverse effect neoplasms Protein Kinase Inhibitors Aged business.industry Middle Aged medicine.disease Confidence interval Regimen 030104 developmental biology Treatment Outcome 030220 oncology & carcinogenesis Neratinib Quinolines Female business medicine.drug |
| Zdroj: | Clinical breast cancer. 19(2) |
| ISSN: | 1938-0666 |
| Popis: | 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 and Methods 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect