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Everolimus improved PFS in patients with metastatic, ER-positive breast cancer
San Antonio Breast Cancer Symposium
SAN ANTONIO — Adding everolimus to exemestane in postmenopausal patients with ER-positive advanced breast cancer improved PFS, according to research presented here.
Study researcher Gabriel N. Hortobagyi, MD, FACP, professor of medicine and chair of the department of breast medical oncology at The University of Texas MD Anderson Cancer Center, said the mammalian target of rapamycin (mTOR) inhibitor showed promising efficacy as a monotherapy and when combined with endocrine therapy in phase 2 trials.
“(The) addition of everolimus to exemestane prolongs PFS in patients with ER-positive, HER-2–negative breast cancer that is refractory to nonsteroidal aromatase inhibitors,” Hortobagyi said. “This benefit is observed in all subgroups. This is the first agent to significantly enhance the efficacy of hormonal therapy in patients with ER-positive breast cancer. This treatment could represent a paradigm shift in the management of this patient population.”
This double blind, placebo-controlled, phase 3 trial evaluated everolimus (Afinitor, Novartis) plus exemestane (Aromasin, Pharmacia and Upjohn) in patients with ER-positive advanced breast cancer refractory to letrozole or anastrozole treatment.
The trial included 724 patients who were randomly assigned 2:1 to exemestane 25 mg/day with everolimus 10 mg/day or placebo. The primary endpoint was PFS, and secondary endpoints included OS, response rate, quality of life and safety.
The median PFS was 7.4 months among patients treated with exemestane plus everolimus vs. 3.2 months for patients treated with exemestane plus placebo. In addition, response rates and clinical benefit rate was higher in patients who received exemestane plus everolimus. In the exemestane plus everolimus group, the most common grade-3 or grade-4 adverse events were stomatitis, anemia, hyperglycemia, dyspnea and fatigue. There was no deterioration in quality of life.
Hortobagyi also said an interim analysis of OS showed that there were more deaths in the placebo arum, but these data are not yet significant because the data are not mature.
Disclosure: Dr. Hortobagyi reports no relevant financial disclosures.
Earn CME this spring at the HemOnc Today Breast Cancer Review & Perspective meeting to be held March 23-24, 2012 at the Hilton San Diego Bayfront. See details at HemOncTodayBreastCancer.com.
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We currently don't have any treatments for patients who have hormone receptor-positive advanced breast cancer other than hormonal therapy. We know that over time, patients become resistant to hormonal therapy. There has been a lot of interest in understanding the biology behind why patients become resistant to hormonal therapy. The thing that we see is that some of the growth factor receptor pathways seem to be activated, and there have been some studies in the laboratory that showed if you block these pathways, you may be able to make hormonal therapies work better and last longer before patients progress. In HER2 positive cancers, we can block HER2 with either trastuzumab or lapatinib. In HER2 negative, we have never really had anything to offer patients other than hormonal therapy. The mTOR protein is a protein that is involved in signal transduction and there is evidence from smaller studies that if you block mTOR you can improve the benefit of hormonal therapy. This was now tested in a very large phase-3 trial that took patients receiving second-line hormonal therapy, and compared exemestane alone to exemestane with everolimus. That showed a very big difference in PFS, more than double. It was a bigger difference than we typically see when we test a new drug in breast cancer. Usually you might extend disease-free survival by 2-4 months, but here it was prolonged by more than 6 months. There is also a sense that it may improve OS, though the final analysis is not out on that yet. This is a big study because it has an impact on disease-free survival and almost certainly will have have an impact on OS as well. We will have to pay attention to the side effects, which did occur more in patients who received everolimus, but the side effects were not severe.
Debasish "Debu" Tripathy, MD
HemOnc Today Editorial Board member
Disclosure: Dr. Tripathy reports no relevant financial disclosures.
For more information:
- Hortobagyi G. #S3-7. Presented at: 2011 CTRC-AACR San Antonio Breast Cancer Symposium; Dec. 6-10; San Antonio.
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