Tamoxifen and aromatase inhibitors (AIs) are the mainstay of therapy for women with hormone receptor-positive (HRP) breast cancer (BC), but what about for postmenopausal women with HRP BC and advanced disease? Is there an advantage of one drug over another?
In this meta-analysis of all four phase III multicenter, international, randomized clinical trials that compared third generation AIs (i.e., exemestane, anastrozole, and letrozole) with tamoxifen 20 mg as first-line endocrine therapy for HRP BC in postmenopausal women with advanced disease, investigators found that AIs were associated with an increase in progression-free survival (PFS) but not overall survival (OS).
The four trials that were included were the European Organisation for Research and Treatment of Cancer (EORTC) group, which evaluated exemestane versus tamoxifen in 371 patients from 81 worldwide centers; Study 0027, which compared the use of anastrazole to tamoxifen in 668 patients in 83 international centers; Study 0030, which studied anastrazole versus tamoxifen in 353 patients at 97 North American centers; and the Femara Study PO25, which analyzed letrozole versus tamoxifen use among 907 patients in 201 centers from 29 countries.
The percentage of women with HRP BC varied across studies from 93% (EORTC trial) to 45% (Study 0027). Deidentified individual patient data were available for the first three studies but not for the letrozole trial. To compensate for this, data including odds ratio or hazard ratio with confidence intervals were obtained from the clinical study report provided by the manufacturer of letrozole.
The focus of this meta-analysis was to determine the following clinical outcomes: clinical benefit rate (CBR), which was defined as the proportion of patients who experienced a best objective response of complete response, partial response, or stable disease for more than 24 weeks; duration of clinical benefit (DoCB); PFS; and OS. DoCB was determined for patients who had achieved clinical benefit (CB). It was assessed as the time it took for the tumor to progress. For CBR, DoCB, and OS, analyses were conducted fitting the model with and without the letrozole.
The researchers found that more patients achieved a CB in the AI group compared with the tamoxifen group (odds ratio 1.56 with the letrozole study; CI, 1.29-1.89 and 1.51 without the letrozole study; CI, 1.11-2.05). DoCB did not reach statistical significance between the groups. Hazard ratios (HRs) were measured for PFS and favored AIs (HR = 0.82; CI, 0.71-0.95). Lastly, OS was similar between the groups with a HR 1.05 (CI, 0.93-1.20) with letrozole and HR 1.06 without letrozole (CI, 0.87-1.29).
The investigators concluded that although AIs put significantly more women into clinical benefit, their tumors were not controlled for significantly longer. Despite being associated with a significant increase in PFS, overall survival was not increased for AIs over tamoxifen.
For pharmacists who provide care for patients with BC, this study helps clarify the role of tamoxifen and AIs in the management of advanced HRP BC in postmenopausal women.
The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.
« Click here to return to Breast Cancer Update.