Professor Michael Gnant told the eighth European Breast Cancer Conference (EBCC-8) that the latest results from the BOLERO-2 trial would change clinical practice. "These results indicate a new standard of care for women with advanced oestrogen receptor positive breast cancer that is resistant to hormonal therapy," he said.
BOLERO-2 had shown previously that the combination of the two drugs significantly improved outcomes, stopping further tumour growth for nearly 11 months, in a group of patients with a form of breast cancer that is highly resistant to treatment. However, as some anti-cancer 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 non-steroidal aromatase inhibitors, for example anastrozole, affected bone strength.
Gnant, Co-ordinator of the Comprehensive Cancer Centre at the Medical University of Vienna, and colleagues from several different countries looked at markers for bone turnover and bone resorption. The rate at which bone forms, degrades and renews itself) in the 724 patients enrolled in the trial and randomised to receive either everolimus and exemestane or exemestane alone (the placebo group. The patients had an average age of 62, were from 24 different countries and had been treated previously with aromatase inhibitors. They were enrolled between June 2009 and January 2011, and the researchers assessed three different bone markers at the time of enrolment and after six and twelve weeks.
They found that levels of all three bone markers decreased significantly after six and 12 weeks for women taking everolimus, indicating a low turnover of bone, which improves bone strength and health. After six weeks, bone-specific alkaline phosphatase (BSAP) had dropped by 5.5 per cent, amino-terminal propeptide of type 1 collagen (P1NP) had dropped by 20.4 per cent, and C-terminal cross-linking telopeptide of type I collagen (CTX) had dropped by 6.3 per cent. After 12 weeks, they had decreased by 3.6 per cent, 26.8 per cent and 0.5 per cent respectively. In the placebo group they all increased.
Overall, out of all the women in the trial, only 3 per cent of the women taking everolimus had further bone metastases after 60 days, compared with 6 per cent in the placebo group. In a sub-group of women who were known to have bone metastases at the start of the trial, everolimus halved the rate of further bone metastases, with bone metastases progressing in nearly 4 per cent of these women, compared to 8 per cent 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.
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.
MEDICA.de; Source: European Cancer Organisation ECCO