Safety and efficacy of neratinib (HKI-272) plus vinorelbine in the treatment of patients with ErbB2-positive metastatic breast cancer pretreated with anti-HER2 therapy |
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| Institution: | 1. Medical Oncology Clinic, Jules Bordet Institute, Brussels University, Brussels;2. Medical Oncology Department, Sint-Augustinus, Antwerp, Belgium;3. Medical Oncology Unit, Hospital Universitario 12 de Octubre, Madrid, Spain;4. Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China;5. Oncology and Internal Medicine Department, City of Hope National Medical Center, Duarte, USA;6. Clinical Investigation Unit, Curie Institute, Paris, France;7. Division of Oncology/Hematology, Columbia University Medical Center, New York, USA;8. Pfizer Global Research and Development, Paris, France;9. Inventiv Clinical Solutions, Cambridge, USA;10. First Chemotherapy Department with Radiotherapy Sub-department, Ziemi Lubelskiej Oncology Center, Lublin, Poland |
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| Abstract: | BackgroundNeratinib (HKI-272) is a potent irreversible pan-ErbB tyrosine kinase inhibitor with clinical activity in patients with ErbB2/HER2-positive breast cancer.Patients and methodsPhase I of this open-label, phase I/II study investigated the maximum tolerated dose (MTD) of oral neratinib (160 or 240 mg/day) plus vinorelbine (25 mg/m2; days 1 and 8 of each 21-day cycle) in patients with solid tumors. Phase II assessed the safety, clinical activity, and pharmacokinetics of the combination in patients with HER2-positive metastatic breast cancer; the primary efficacy end point was objective response (OR).ResultsIn phase I (n = 12), neratinib (240 mg) plus vinorelbine (25 mg/m2) was established as the MTD. In phase II, 79 patients with HER2-positive metastatic breast cancer were treated at the MTD. The most common treatment-related adverse events were diarrhea (96%), neutropenia (54%), and nausea (50%). Three patients discontinued treatment due to diarrhea. No clinically important skin side-effects were observed. The OR rate in assessable phase II patients was 41% (no prior lapatinib) and 8% (prior lapatinib). There was no evidence of pharmacokinetic interaction between neratinib and vinorelbine.ConclusionNeratinib plus vinorelbine showed promising antitumor activity and no unexpected toxic effects in HER2-positive metastatic breast cancer patients.Trial registrationClinicalTrials.gov #NCT00706030. |
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