Adding the drug everolimus (Afinitor) to trastuzumab (Herceptin) can improve treatment response to trastuzumab-based therapies in some women with HER2-positive metastatic breast cancer.

In the phase I/II trial yielding these results, the combined use of the two agents was studied in 47 women with HER2-overexpressing metastatic breast cancer that progressed on trastuzumab-based therapy.

“Herceptin works well for many patients, but about 30% of those with advanced disease do not respond to the drug, even combined with chemotherapy,” explained Phuong Khanh Morrow, MD—lead coauthor of the study and an assistant professor in the department of breast medical oncology at The University of Texas M. D. Anderson Cancer Center in Houston—in a statement announcing the study results, which were presented online by the Journal of Clinical Oncology. “Even if metastatic HER2-positive breast cancer initially responds to Herceptin, the disease usually eventually progresses on standard Herceptin-based therapy.”

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Trastuzumab resistance has been linked to activation of the mammalian target of rapamycin (mTOR) cancer pathway. However, everolimus overcomes resistance by inhibiting mTOR.

The study subjects received everolimus daily and trastuzumab every 3 weeks. The combination treatment resulted in a clinical benefit rate of 34%, providing partial response in seven patients (15%) and persistent stable disease (lasting 6 months or longer) in nine (19%). Median progression-free survival was 4.1 months. The main nonhematologic toxicities associated with the regimen were fatigue, infection, and mucositis.

“Inhibition of mTOR results in clinical benefit and disease response in patients with trastuzumab-resistant HER2-overexpressing [metastatic breast cancer].”