In oestrogen-receptor (ER) positive women with advanced breast cancer, combining everolimus (EVE) with exemestane (EXE) reduces bone turnover and disease progression in the bone. This was shown during the 2012 European Breast Cancer Congress (EBCC) by the updated results from the randomised controlled BOLERO-2 study.
BOLERO-2 previously demonstrated that the combination of EXE and EVE significantly improves outcomes, stopping further tumor growth for nearly 11 months, in a group of breast cancer patients that is highly resistant to treatment. However, previous studies indicate that some anti-cancer drugs are associated with decreased bone mineral density and an increased risk of fractures. As such it was important to discover whether the combination of EXE and EVE used with or after treatment with other drugs such as non-steroidal aromatase inhibitors, has an effect on bone health. In this light, researchers evaluated the bone turnover and bone resorption in the 724 patients enrolled in BOLERO-2. Three different bone markers (i.e. BSAP, CTX and P1NP) were assessed at the time of enrollment and after 6 and 12 weeks.
The presented data showed that the levels of all three bone markers were decreased significantly after 6 and 12 weeks for women taking EVE, indicating a low bone turnover, which in turn improves bone strength and health. After six week the BSAP level dropped by 5.5%, the P1NP level dropped by 20.4% and the CTX level was reduced with 6.3%. After 12 weeks, the three markers had dropped by 3.6%, 26.8% and 0.5% respectively. In the placebo group on the other hand, all bone marker levels had increased. After 60 days of treatment, only 3% of the EVE+EXE treated patients displayed further bone metastases, compared with 6% in the placebo group. Furthermore, in the subgroup of women with bone metastases at baseline, bone metastases progressed in nearly 4% in the EXE+EVE arm compared with 8% in the EVE only group. Importantly, this trend continued to be visible for longer than 6 months. In total, 2.1% of the patients in the EXE+EVE arm suffered a bone fracture compared with 3.4% in the placebo arm.
According to the investigators, these results show that adding EVE to EXE is greatly beneficial to bone health by reducing bone turnover and improving the time to bone metastases and the time to progression of existing bone metastases. As such, EVE seems to make it more difficult for metastases to grow in the bone. In addition to the effect on outcome and time to progression this improved bone health is an important benefit of combining EXE with EVE. Currently a clinical trial is being designed to assess the effect of EVE in women with early breast cancer, where bone health may be even more important.
Gnant et al. Everolimus added to exemestane reduced bone markers and disease progression in bone in postmenopausal women with advanced breast cancer: updated results from the BOLERO-2 trial. Presented at EBCC 2012; Abstract LBA3.