Neratinib in combination with trastuzumab for the treatment of advanced breast cancer: a phase I/II study

Details

Serval ID
serval:BIB_D35E480745F3
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Collection
Publications
Institution
Title
Neratinib in combination with trastuzumab for the treatment of advanced breast cancer: a phase I/II study
Title of the conference
2009 ASCO Annual Meeting
Author(s)
Swaby R., Blackwell K., Jiang Z., Sun Y., Dieras V., Zaman K., Zacharchuk C., Powell C., Abbas R., Thakuria M.
Address
Orlando, Florida, May 29 - June 2, 2009
ISBN
0732-183X
Publication state
Published
Issued date
2009
Volume
27
Series
Journal of Clinical Oncology
Pages
1004
Language
english
Notes
Background: Neratinib (HKI-272) is an orally administered irreversible pan-ErbB receptor tyrosine kinase inhibitor. In an ongoing phase II study, the preliminary objective response rate was 26% in patients with ErbB2+ advanced breast cancer with prior trastuzumab therapy. This study assessed the safety and preliminary efficacy of the combination of neratinib plus trastuzumab. Methods: Patients with advanced ErbB2+ breast cancer that progressed following trastuzumab therapy were enrolled. The primary endpoint was 16-week progression free survival rate (PFS). In part 1 (dose escalation), patients received neratinib 160 mg or 240 mg daily plus trastuzumab 4 mg/kg IV loading dose then 2 mg/kg weekly. In part 2, patients received weekly trastuzumab with neratinib 240 mg daily. Timed blood samples were collected for PK analyses. PK analysis is ongoing. Results: 45 patients (part 1 n = 8; part 2 n = 37) were enrolled (mean age 52 yr); 9 are active. In part 1, cohorts 1 and 2 were fully enrolled with 4 patients each. No dose limiting toxicities were observed. Most common AEs, any grade, were diarrhea (91%), nausea (51%), anorexia (40%), vomiting (38%), and asthenia (27%). Grade 3/4 AEs were diarrhea (13%), nausea (4%), vomiting (4%). Two patients receiving neratinib 240 mg reported AEs leading to withdrawal. No AEs of congestive heart failure and no significant drops of left ventricular ejection fraction were reported. Among 33 patients evaluable for efficacy, objective response rate was 27% (95% CI, 13% - 46%); 16-week PFS rate (for part 2) 47% (95% CI, 29% - 63%); median PFS was 19 weeks (95% CI 15 - 32 weeks). Conclusions: Neratinib plus trastuzumab was well tolerated with no significant or unexpected toxicities, and demonstrated clinical activity.
Create date
11/06/2009 10:50
Last modification date
20/08/2019 15:53
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