LETTER TO THE EDITOR.
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
Data discussed in this letter were presented at the 2012 American Society of Clinical Oncology Annual Meeting; June 1-5, 2012; Chicago, IL (Abstracts 551 and 559); and at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium; December 4-8, 2012; San Antonio, TX (Poster P6-04-02). Everolimus in Elderly Hormone- Receptor—Positive Breast Cancer Patients.
Author Disclosures: Dr Rogerio reports employment with Novartis Pharmaceuticals Corporation, which funded this study.
Authorship Information: Concept and design; acquisition of data; critical revision of the manuscript for important intellectual content.
Address correspondence to: Jaqueline Rogerio, MD, Senior Medical Director, Novartis Pharmaceuticals Corporation, 1 Health Plaza, East Hanover, NJ 07936. E-mail: jaqueline .firstname.lastname@example.org.
1. Piccart M, Baselga J, Noguchi S et al. Final progression-free survival analysis of BOLERO-2: a phase III trial of everolimus for postmenopausal women with advanced breast cancer. Presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium; December 4-8, 2012; San Antonio, TX.
2. Pritchard KI, Burris HA, Rugo HS et al. Safety of everolimus for women over 65 years of age with advanced breast cancer (BC): 18-month follow-up of BOLERO-2 2012. Presented at the 2012 American Society of Clinical Oncology Annual Meeting; June 1-5, 2012; Chicago, IL.
3. Piccart-Gebhart MJ, Noguchi S, Pritchard KI, et al. Everolimus for postmenopausal women with advanced breast cancer: updated results of the BOLERO-2 phase III trial. J Clin Oncol. 2012;30:abstract 559.
4. Drugs: everolimus. FDA website. www.fda.gov/drugs/informationondrugs/approveddrugs/ucm313008.htm. Published July 23, 2012. Accessed September 12, 2012.