A pivotal Phase III study shows everolimus tablets plus exemestane, a hormonal therapy, more than doubled the time women lived without tumor growth (progression-free survival; PFS) and significantly reduced the risk of cancer progression by 57% versus exemestane alone in patients with advanced breast cancer1.
“The magnitude of benefit seen in these patients, despite their resistance to previous hormonal therapies, shows everolimus represents a potential important new treatment approach.” BOLERO-2 (Breast cancer trials of OraL EveROlimus-2) examined the safety and efficacy of everolimus in combination with exemestane versus exemestane alone in postmenopausal women with ER+HER2- advanced breast cancer who recurred or progressed while on or following previous treatment with hormonal therapies, letrozole or anastrozole1. Findings from the trial will be presented today during a Presidential Symposium at the 2011 European Multidisciplinary Cancer Congress in Stockholm, Sweden.
At a pre-planned analysis, the trial met its primary endpoint of PFS showing treatment with everolimus improved PFS to 6.9 months compared to 2.8 months (hazard ratio 0.43 [95% confidence interval (CI): 0.35 to 0.54]; p<0.0001) by local investigator assessment. This significant improvement was consistent across all subgroups including number of prior therapies, presence of visceral disease, bone metastases and prior use of chemotherapy1. Hormonal therapy remains the cornerstone of treatment for women with advanced breast cancer but most women with metastatic disease do not respond to initial treatment with hormonal therapy, and almost all initial responders develop resistance2,3. Additionally, life expectancy is significantly shortened due to the worsening of the disease3. Everolimus targets mTOR in cancer cells, a protein that acts as an important regulator of tumor cell division, blood vessel growth and cell metabolism4. Resistance to hormonal therapy in breast cancer has been associated with over-activation of the mTOR pathway3. Data from BOLERO-2 support worldwide regulatory submissions, which are planned by the end of 2011. Additional data from BOLERO-2 will be presented at upcoming medical congresses this year. Worldwide, there are approximately 220,000 newly diagnosed cases of ER+HER2- advanced breast cancer each year5,6. Everolimus is also being investigated for the treatment of patients with HER2+ advanced breast cancer7,8.
1 Baselga J. Everolimus in combination with exemestane for postmenopausal women with advancedbreast cancer who are refractory to letrozole or anastrozole: results of the BOLERO-2 phase III trial.2011 European Multidisciplinary Cancer Congress. Presentation of late breaking abstract No. 9LBA.September 26, 2011.
2 Gonzalez-Angulo A. Overview of Resistance to Systematic Therapy in Patients with Breast Cancer.Breast Cancer Chemosensitivity. Available at http://www.ncbi.nlm.nih.gov/books/NBK6306/. AccessedSeptember 2011.
3 Johnston SR. New strategies in estrogen receptor-positive breast cancer. Clin Cancer Res 2010;16:1979-87.
4 Motzer, et. al. Phase 3 Trial of Everolimus for Metastatic Renal Cell Carcinoma. Cancer 2010 Sep;116(18):4256-4265.
5 Buckley N et al. Decision Resources: Breast Cancer Event Driven. March 2011.
6 World Cancer Report. International Agency for Research on Cancer. Available at http://globocan.iarc.fr/factsheets/populations/factsheet.asp?uno=900. Accessed September 2011.
7 Everolimus in Combination With Trastuzumab and Paclitaxel in the Treatment of HER2 Positive LocallyAdvanced or Metastatic Breast Cancer (BOLERO-1). Available at http://www.clinicaltrials.gov/ct2/show/NCT00876395?term=bolero-1&rank=1. Accessed September 2011.
8 Daily Everolimus in Combination With Trastuzumab and Vinorelbine in HER2/Neu Positive Women WithLocally Advanced or Metastatic Breast Cancer (BOLERO-3). Available at http://www.clinicaltrials.gov/ct2/show/NCT01007942?term=bolero-3&rank=1. Accessed September 2011.