Updated BOLERO-2 Data Support Efficacy of Everolimus in Breast Cancer

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Updated results from the BOLERO-2 trial support the study's earlier findings that mTOR kinase inhibitor everolimus improves survival for postmenopausal patients with breast cancer.

Hope S. Rugo, MD

Updated results from the BOLERO-2 trial support the study’s earlier findings that mTOR kinase inhibitor everolimus improves survival for postmenopausal patients with breast cancer, according to 18-month follow-up data presented at the American Society of Clinical Oncology (ASCO) Breast Cancer Symposium on September 14.

The updated investigator assessment of the progression-free survival (PFS) rate for patients treated with exemestane and everolimus was 7.8 months compared to 3.2 months for those treated with exemestane alone (hazard ratio = 0.45, 95% CI: 0.38-0.54, P < 0.0001).

Independent reviewers assessed PFS at 11.0 months for patients taking the drug combination, as compared to 4.1 months for those taking exemestane alone (hazard ratio = 0.38, 95% CI: 0.31-0.48, P < 0.0001).

“These results represent a significant advance in the search for ways to improve response to hormone therapy, and counteract acquired resistance,” said Hope S. Rugo, MD, an author of the follow-up study, who presented the results. Rugo is a professor of medicine and director of breast oncology and clinical trials education at the University of California San Francisco Helen Diller Family Comprehensive Cancer Center.


The phase III BOLERO-2 trial enrolled 724 postmenopausal women with hormone receptor-positive metastatic breast cancer who had progressed on a nonsteroidal aromatase inhibitor (AI), such as anastrozole or letrozole. Eligible women were treated with a daily 25 mg dose of exemestane and randomized (2:1) to 10 mg everolimus or placebo.

Women treated with everolimus combined with exemestane compared to exemestane alone showed significant progression-free survival benefits. Based on those results, the FDA approved everolimus in combination with exemestane in July.

“We await the mature survival data from this study, as well as additional studies that are planned or underway,” Rugo said.

A subanalysis of the BOLERO-2 trial that was also presented at the Breast Cancer Symposium examined disease progression in bone and bone markers in patients with bone metastases. After 60 days, the cumulative incidence rate of progressive disease in bone was lower in women treated with exemestane and everolimus (6.16%) compared to exemestane and placebo (3.03%). The trend continued beyond 6 months.

At 6 and 12 weeks, bone marker levels increased versus the baseline with exemestane and placebo patients but decreased in those treated with exemestane and everolimus. Bone-related adverse events were reported with similar frequencies in both groups (everolimus = 2.9%, placebo = 3.8%) and were reported as grades 1 or 2.

“For breast cancer patients with bone metastases who have not responded to non-steroidal AIs, this study may provide another option for the management of their disease,” Anees B. Chagpar, MD, MSc, MA, MPH, said in a statement. Chagpar is the director of the Breast Center at Smilow Cancer Hospital at Yale-New Haven.

Preclinical studies found a correlation between mTOR inhibition and decreased osteoclast survival and activity. The BOLERO-2 study analyzed the difference in bone marker levels and breast cancer progression between women who had bone metastases at baseline and were treated with everolimus versus placebo.