Phase I/II study of trastuzumab in combination with everolimus (RAD001) in patients with HER2-overexpressing metastatic breast cancer who progressed on trastuzumab-based therapy Full Text
Journal of Clinical Oncology, 07/08/2011
Clinical Article
Morrow PK et al. – Inhibition of mTOR results in clinical benefit and disease response in patients with trastuzumab-resistant HER2-overexpressing MBC.
Methods- Pooled analysis (n = 47), stemming from two trials that occurred concurrently in The University of Texas MD Anderson Cancer Center, Beth Israel Deaconess Medical Center, and Dana-Farber Cancer Institute
- Patients with HER2-overexpressing MBC who had progressed on trastuzumab-based therapy received trastuzumab every 3 weeks in combination with daily everolimus
- Among 47 patients, combination of everolimus and trastuzumab provided partial responses in 7 patients (15%) and persistent stable disease (lasting 6 months or longer) in 9 patients (19%), resulting in clinical benefit rate of 34%
- Median PFS 4.1 month
- Fatigue, infection, and mucositis were predominant nonhematologic toxicities
- Trastuzumab did not have significant influence on pharmacokinetic profile of everolimus
- Patients with PTEN loss demonstrated decreased OS (P = .048)
- PFS not affected by PTEN loss
