ASCO 2013: Everolimus Significantly Delays Tumor Growth in Women with HER2-positive Advanced Breast Cancer
The addition of everolimus (Afinitor), an mTOR inhibitor, to trastuzumab (Herceptin) and vinorelbine significantly extended progression-free survival in women with HER2-positive advanced breast cancer, compared to treatment with placebo plus trastuzumab and vinorelbine, in the phase III BOLERO-3 trial (Breast cancer trials of OraLEveROlimus-3). The study enrolled women who received prior taxane therapy and whose disease was resistant to prior trastuzumab treatment. The study results were presented today at the 2013 ASCO Annual Meeting (Abstract 505).
Primary Endpoint
Final progression-free survival data showed that adding everolimus to the standard treatment of trastuzumab and vinorelbine reduced the risk of disease progression by 22% (hazard ratio = 0.78 [95% confidence interval = 0.65–0.95], P < .01), meeting the study’s primary endpoint. Median time to disease progression was 7.0 months in the everolimus combination arm and 5.8 months in the placebo combination arm.
All patients were resistant to trastuzumab-containing regimens, and 27% of the patient population was pretreated with a lapatinib (Tykerb)-containing regimen. Findings on overall survival, the key secondary endpoint of the trial, are not yet mature.
"These encouraging data demonstrate that everolimus has a meaningful impact in heavily pretreated HER2-positive advanced breast cancer patients," said Ruth M. O’Regan, MD, Professor and Vice-Chair for Educational Affairs, Department of Hematology and Medical Oncology, Emory University School of Medicine, and lead study author. "Everolimus works differently than available treatment options for HER2-positive advanced breast cancer by inhibiting mTOR, and may offer an important new option for physicians and their patients."
Safety Profile
Adverse events were consistent with the known safety profile of everolimus. The most common all-grade adverse reactions (incidence > 30%) were neutropenia, stomatitis, anemia, leukopenia, fatigue, pyrexia, diarrhea, nausea, decreased appetite, and constipation. The most common grade 3/4 adverse reactions (incidence > 2%) were neutropenia, leukopenia, anemia, stomatitis, fatigue, febrile neutropenia, diarrhea, pyrexia, nausea, hyperglycemia, and thrombocytopenia.
The number of on-treatment deaths (2.5% per arm), and the number of deaths due to adverse events (0.7% per arm) were similar across treatment groups.
Dr. O’Regan has served in a consulting or advisory role for Novartis, and has received research funding from Genentech and Novartis.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
