Everolimus in Elderly Hormone-Receptor–Positive Breast Cancer Patients
To the Editors:
I read with great interest the article entitled “Breast Cancer: Will Treatment Costs Outpace Effectiveness?” by MP Zimmerman et al, published in the December 2012 issue (Volume 18, Special Issue 5, SP200-SP202) of The American Journal of Managed Care. In response to the authors’ discussion regarding the potential for treatment costs to outpace effectiveness in breast cancer, I would like to provide clarification, specifically with respect to the effectiveness of everolimus combined with exemestane to treat patients older than 65 years.
The authors accurately reported the overall results from BOLERO-2, a phase III trial (N = 724) with everolimus, a mammalian target of rapamycin (mTOR) inhibitor, in postmenopausal women with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC) that was refractory to nonsteroidal aromatase inhibitors (NSAIs). Results of this trial show that treatment with everolimus plus exemestane improved progression- free survival (PFS) by 4.6 months, from 3.2 months with exemestane alone to 7.8 months with the combination therapy (local assessment, hazard ratio: 0.45; 95% CI: 0.38-0.54; P <0.0001).1 Although overall survival at the time of interim analysis was not mature, results at the median 18-month follow- up assessment showed that fewer deaths occurred among patients treated with everolimus plus exemestane compared with those treated with exemestane alone (25.4% vs 32.2%).1
Exploratory subgroup analysis of the BOLERO-2 trial at a median 18-month follow-up visit showed that for patients younger than 65 years and patients 65 years and older, improvements in PFS, overall response rate (ORR), and clinical benefit rate (CBR) were observed with everolimus + exemestane versus placebo + exemestane (Table 1).2 Additionally for patients younger than 70
years and 70 years and older, improvements in PFS ORR and CBR were observed with everolimus + exemestane versus placebo + exemestane (Table 1). The safety profile of EVE + EXE in elderly patients with advanced BC was consistent with the known overall profile of each agent.2
In conclusion, contrary to the claim put forth by Zimmerman et al, results from the BOLERO-2 trial show that patients younger than 65 years and those 65 years and older with HR+ HER2– BC
have the potential to benefit from treatment with everolimus + exemestane. Currently, everolimus, in combination with exemestane, remains the only mTOR inhibitor approved by the FDA for managing patients with HR+ HER2–BC that is refractory to NSAI therapy.
Response From The Authors
Thank you for your somewhat belated comments on our article, “Breast Cancer: Will Treatment Costs Outpace Effectiveness?”, published in the December 2012 issue (Volume 18, Special Issue 5, SP200-SP202) of The American Journal of Managed Care. The information presented in the article from the BOLERO-2 study was acquired from information cited in the abstract by Martine J. Piccart-Gebhart, et al, presented at the June 2012 American Society of Clinical Oncology meeting and the press release from the FDA on July 23, 2012, announcing that it had approved everolimus.3,4 The information available at the time showed that everolimus had an overall positive effect when used in combination therapy for breast cancer. These 2 references did not contain any efficacy results stratified by age.
Additional subgroup analysis is quite often performed after initial results of trials are presented. These subgroup analyses many times identify efficacy and safety information that is valuable to clinicians in treating and managing their patients. Thank you for providing further valuable information that will assist clinicians in determining optimal therapy for their patients.
Marj P. Zimmerman
Stanton R. Mehr