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`'Strongest Ever Data' in Breast Cancer With Everolimus
`September 26, 2011
`Zosia Chustecka
`September 26, 2011 (Stockholm, Sweden) — The combination of everolimus (Afinitor, Novartis) plus exemestane has
`produced "the strongest data ever seen in estrogenreceptor [ER]positive breast cancer," principal investigator José
`Baselga, MD, from the Massachusetts General Hospital and Harvard Medical School, Boston, told Medscape Medical
`News.
`
`The data come from a pivotal phase 3 study, known as BOLERO2, which was stopped early because of the benefit
`observed. Results were unveiled here at the 2011 European Multidisciplinary Cancer Congress.
`
`"Everolimus is the most important advance in breast cancer since trastuzumab," said Fabrice André, MD, from the
`Institut Gustave Roussy, Paris, France, who acted as discussant. "The data are robust and are clinically relevant," he
`said, adding that "the efficacy is in the range of the most important recent advances in the field of medical oncology."
`
`Data from the study will now be submitted for approval, and clinicians should wait for
`registration before they incorporate this new drug combination into clinical practice, Dr.
`Baselga told Medscape Medical News.
`
`However, because both drugs are already commercially available, they could be used offlabel
`for this new indication. Everolimus is an mTOR inhibitor that has already been approved in
`the United States for the treatment of progressive neuroendocrine tumors of pancreatic origin
`and advanced renal cell carcinoma in certain patients. Exemestane is an aromatase inhibitor,
`already widely used as adjuvant therapy for ERpositive breast cancer. Both drugs are taken
`orally.
`
`Rationale for This Approach
`
`Dr. José Baselga
`
`Previous smaller studies and preclinical data support the use of an mTOR inhibitor to reverse the resistance that
`develops to hormonal therapy in ERpositive breast cancer, Dr. Baselga noted. That resistance has been associated
`with an activation of the mTOR pathway, which is inhibited by drugs such as everolimus.
`
`The results from this large phase 3 trial show that "everolimus is the first agent to enhance hormone therapy in
`refractory ERpositive breast cancer patients," and they represent a "paradigm shift in the management of these
`patients," he told delegates.
`
`The BOLERO2 study was conducted in 724 postmenopausal women with ERpositive but HER2negative advanced
`breast cancer who had previously been treated with and had become refractory to the nonsteroidal aromatase inhibitors
`letrozole and anastrozole. Previous therapies included tamoxifen (in 48% patients), fulvestrant (in 16%), and
`chemotherapy (in 68%).
`
`"When patients stop responding to hormonal therapy, the benefits from any secondary therapy are limited," Dr.
`Baselga explained.
`
`All of the women in the study received exemestane, which is a steroidal aromatase inhibitor with a slightly different
`profile than letrozole or anastrozole. In addition, women were randomized in a 2:1 ratio to receive everolimus
`(10 mg/day orally).
`
`A preplanned interim analysis found that everolimus significantly improved progressionfree survival, the primary end
`point of the study. Median progressionfree survival, assessed by local investigators, was longer with everolimus plus
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`exemestane than with exemestane alone (6.9 vs 2.8 months; hazard ratio [HR], 0.43; P ≤ .0001). These figures
`changed slightly after central assessment (10.6 vs 4.1 months; HR, 0.36; P < .0001).
`
`These results were highly significant, Dr. Baselga emphasized. "This is a very uncommon result in metastatic disease,"
`he said at a press briefing. "Very seldom do you see such an effect."
`
`In addition, there was a significantly greater response rate (9.5% vs 0.4%) and clinical benefit (33.4% vs 18.0%) in the
`combination group. Dr. Baselga noted that these data are immature and likely to improve.
`
`The most common adverse effects reported in the combination and exemestanealone groups were stomatitis (8% and
`1%, respectively), anemia (5% and 1%), dyspnea (4% and 1%), hypoglycemia (4% and <1%), fatigue (3% and 1%), and
`pneumonitis (3% and 0%).
`
`"The safety profile is consistent with previous everolimus experience," Dr. Baselga explained.
`
`In a statement from the manufacturer, Novartis Oncology president Herve Hoppenot said: "Everolimus is the first drug
`to show significant efficacy when combined with hormone therapy in ERpositive and HER2negative breast cancer,
`where there continues to be a critical unmet need."
`
`"The magnitude of benefit seen in these patients, despite their resistance to previous hormonal therapies, shows that
`everolimus represents a potential important new treatment approach," he added.
`
`This BOLERO2 trial was funded by Novartis. Dr. Baselga reports acting as a consultant for many pharmaceutical
`companies, including Novartis, Roche, Merck SA, and Bayer.
`
`2011 European Multidisciplinary Cancer Congress (EMCC): Abstract 9LBA. Presented September 26, 2011.
`
`Medscape Medical News © 2011 WebMD, LLC
`
`Send comments and news tips to news@medscape.net.
`
`Cite this article: 'Strongest Ever Data' in Breast Cancer With Everolimus. Medscape. Sep 26, 2011.
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