The Phase II study evaluated the safety and efficacy of a daily 240mg oral dose of neratinib in 136 women diagnosed with ErbB-2-positive locally advanced or metastatic breast cancer. The primary end point of the open-label, two-arm study was the 16-week progression-free survival (PFS) rate. Secondary end points included safety, objective response rate and clinical benefit rate.
Patients were assigned to one of two study arms based on prior treatment with trastuzumab, the standard of care for the treatment of advanced ErbB-2-positive breast cancer. Women enrolled in arm A (n=66) had either previously received at least six weeks of standard trastuzumab treatment or had experienced disease progression during or following trastuzumab-containing adjuvant therapy. Women in arm B (n=70) received no prior treatment with any ErbB-2-targeted therapy, including trastuzumab.
The efficacy analysis included 127 evaluable patients, 61 in arm A and 66 in arm B. In patients who were previously treated with trastuzumab (arm A), the 16-week PFS rate was 60%, and the median PFS was 23 weeks, as evaluated by independent assessment.
According to the company, the objective response rate was 26%, and the clinical benefit rate was 36%. In patients who had not received trastuzumab treatment (arm B), the 16-week PFS rate was 77%, and the median PFS was 40 weeks by independent assessment. The objective response rate was 56%, and the clinical benefit rate was 68%.
Neratinib is an investigational orally-administered potent and irreversible dual inhibitor of the HER-2 and EGFR kinases. Wyeth expects to initiate the first study in a global Phase III program for neratinib in advanced HER-2-positive breast cancer later in December 2008.
Gary Stiles, chief medical officer of Wyeth, said: These Phase II data provide important insight into the potential clinical utility of neratinib in HER2-positive breast cancer.