Jerusalem G, et al. - Researchers compared the therapeutic efficacy of everolimus plus exemestane to that of everolimus alone and capecitabine alone in postmenopausal women with endocrine therapy–resistant, estrogen receptor–positive advanced breast cancer. They found that everolimus plus exemestane, compared with everolimus alone, provided better progression-free survival (PFS), and continued use of this combination in this setting was supported. They found that capecitabine was favored over combination therapy based on the observed numerical PFS difference, though imbalances among baseline parameters and potential informative censoring might have contributed to the PFS outcomes observed with capecitabine. This combination therapy carried no new safety concerns.

Methods

• In this open-label, randomized, phase 2 trial, treatment impacts were assessed in postmenopausal women with advanced breast cancer that had progressed during treatment with nonsteroidal aromatase inhibitors.
• Randomization of patients to three treatment regimens (everolimus 10 mg/day plus exemestane 25 mg/day, everolimus alone 10 mg/day, and capecitabine alone 1250 mg/m² twice daily) was done.
• Main outcomes included estimated hazard ratios (HRs) of progression-free survival (PFS) for everolimus plus exemestane vs everolimus alone (primary objective) or capecitabine alone (key secondary objective), with safety being a secondary objective, with no formal statistical comparisons were planned.

Results

• This study included 309 postmenopausal women, with a median age of 61 years (range, 32-88 years).
• Of these, everolimus plus exemestane was given to 104, everolimus alone was given to 103, and capecitabine alone was given to 102.
• The median follow-up was 37.6 months, from randomization to the analysis cutoff (June 1, 2017).
• Findings demonstrated an estimated HR of PFS was 0.74 (90% CI, 0.57-0.97) for the primary objective of everolimus plus exemestane vs everolimus alone and 1.26 (90% CI, 0.96-1.66) for everolimus plus exemestane vs capecitabine alone.
• Researchers observed potential informative censoring between treatment arms, and they used a stratified multivariate Cox regression model to account for imbalances in baseline characteristics.
• They found a consistent HR for everolimus plus exemestane vs everolimus (0.73; 90% CI, 0.56-0.97), but for everolimus plus exemestane vs capecitabine, the HR was closer to 1 (1.15; 90% CI, 0.86-1.52).
• With capecitabine (74%; n = 75) vs everolimus plus exemestane (70%; n = 73) or everolimus alone (59%; n = 61), more frequent grade 3 to 4 adverse events were seen.