(ChemotherapyAdvisor) – The combination of everolimus plus exemestane reduced bone turnover markers and halved rate of further bone metastases compared with exemestane alone in postmenopausal women with advanced breast cancer during the first 12 weeks of therapy, results of the BOLERO-2 study presented during the 8th European Breast Cancer Conference in Vienna, Austria, March 23 concluded.

“These results indicate a new standard of care for women with advanced estrogen receptor positive breast cancer that is resistant to hormonal therapy,” Prof. Michael Gnant, of the Comprehensive Cancer Centre at the Medical University of Vienna.

Previously, BOLERO-2 had shown that everolimus plus exemestane significantly improved outcomes in patients with breast cancer highly resistant to treatment. However, as some anticancer drugs are associated with reduced bone mineral density and an increased risk of fractures, it was important to discover whether everolimus and exemestane, used with or after treatment with other drugs such as nonsteroidal aromatase inhibitors (e.g., anastrozole), affected bone strength.

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Between June 2009 and January 2011, the multinational, double-blind, placebo-controlled, Phase 3 BOLERO-2 study randomized 724 postmenopausal women with estrogen receptor-positive advanced breast cancer refractory to letrozole or anastrozole 2:1 to receive everolimus 10mg/day plus exemestane 25mg/day (n=485) or exemestane 25mg/day alone (n=239). Median patient age was 62 years; 56% had visceral involvement and 84% were sensitive to prior hormone therapy. At study entry, 76% of patients in the everolimus plus exemestane group had bone metastases vs. 75% in the exemestane alone group and 45% and 55%, respectively, used bisphosphonates at baseline.

Median duration of progression-free survival, the primary end point, was 7.4 months for the combination group vs. 3.2 months for exemestane alone (HR=0.44) by investigator assessment and 11.0 vs. 4.1 months (HR=0.36) by central assessment.

At six weeks, everolimus plus exemestane resulted in a 5.5% decrease in bone-specific alkaline phosphatase, a 20.4% decrease in amino-terminal propeptide of type I collagen, and a 6.3% decrease in C-terminal cross-linking telopeptide of type I collagen. At 12 weeks, this reduction was 3.6%, 26.8% and 0.5%, respectively. In the exemestane alone group, these markers all increased.

Of all women in the trial, 3% of the women taking everolimus had further bone metastases after 60 days vs. 6% in the placebo group; in a subgroup of women who had bone metastases, everolimus halved the rate of further bone metastases; bone metastases progressed in nearly 4% of these women vs. 8% in the placebo group. This trend continued for longer than six months. Any bone-related side effects were rare, and those that did occur were of a low grade, including bone pain and fractures.

“In addition to the spectacular effect on outcomes and time to progression, both in bone and elsewhere, improving bone health is an important aspect of giving patients the best possible treatment,” Prof. Gnant said. “We would now recommend everolimus, in addition to exemestane, for all postmenopausal women with hormone-resistant advanced cancer until further progression of their cancer. The interesting question we would like to address now is the effect of everolimus in women with early breast cancer, where bone health may be an even more important issue. Currently, clinical trials to investigate this are being designed.”

Abstract (Select “Friday 23” and enter Gnant” in the author box to search for Late Breaking Abstract No. 3)