Outcomes from the BOLERO-2 clinical trial show that combining 2 cancer drugs, everolimus and exemestane, significantly improve bone strength and reduce the chances of cancer metastasizing in the bone.
According to Professor Michael Gnant, these latest results from the phase 3 trial will change clinical practice. “These results indicate a new standard of care for women with advanced estrogen receptor positive breast cancer that is resistant to hormonal therapy,” he said.
BOLERO-2 had shown previously, in a group of patients with a form of breast cancer that is highly resistant to treatment, that the combination of the 2 drugs stopped further tumor growth for nearly 11 months. However, because reduced bone mineral density and an increased risk of fractures are associated with some anticancer drugs, it was important to discover how everolimus and exemestane affected bone strength.
Along with Professor Gnant, Coordinator of the Comprehensive Cancer Centre at the Medical University of Vienna (Vienna, Austria), colleagues from several different countries examined markers for bone turnover and bone resorption in the 724 patients enrolled in the trial. Randomized to receive either everolimus and exemestane or exemestane alone (the placebo group), patients averaged 62 years of age, were from 24 different countries, and had previously been treated with aromatase inhibitors. Researchers assessed 3 different bone markers at the time of enrolment and after 6 and 12 weeks.
All 3 bone marker levels decreased significantly after 6 and 12 weeks for women taking everolimus. This indicated an improvement bone strength and health due to low turnover of bone. After 6 weeks, bone-specific alkaline phosphatase (BSAP) had dropped by 5.5%, amino-terminal propeptide of type 1 collagen (P1NP) had dropped by 20.4%, and C-terminal cross-linking telopeptide of type I collagen (CTX) had dropped by 6.3%. They had decreased by 3.6%, 26.8% and 0.5%, respectively, after 12 weeks. All markers had increased in the placebo group.
Overall, after 60 days, only 3% of the women taking everolimus had further bone metastases, compared with 6% in the placebo group. Furthermore, in a subgroup of women with known bone metastases at the beginning of the trial, everolimus cut the rate of further bone metastases in half. Bone metastases progressed in nearly 4% of these women, compared with 8% in the placebo group.
Professor Gnant said, “These results show that the addition of everolimus to exemestane is greatly beneficial to bone health by reducing bone turnover and improving time to bone metastases. Everolimus appears to make it more difficult for metastases to occur and grow in bone.
“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. We would now recommend everolimus, in addition to exemestane, for all post-menopausal 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.”
Source: ECCO.