Jerusalem G, et al. - Researchers assessed the clinical benefit of everolimus in combination with exemestane vs everolimus or capecitabine monotherapies for endocrine therapy–resistant, estrogen receptor–positive advanced breast cancer. They found that everolimus-exemestane combination therapy offered a progression-free survival (PFS) benefit vs everolimus alone and, thus, is supported for continued use in this setting. The authors recommend cautiously interpreting a numerical PFS difference with capecitabine vs everolimus plus exemestane owing to imbalances among baseline characteristics and potential informative censoring.

Methods

• In this open-label, randomized, phase 2 trial, researchers determined treatment effects in postmenopausal women with advanced breast cancer that had progressed during treatment with nonsteroidal aromatase inhibitors.
• Three treatment regimens were randomly administered to patients:
• Everolimus (10 mg/day) plus exemestane (25 mg/d);
• Everolimus alone (10 mg/day); and
• Capecitabine alone (1,250 mg/m² twice daily).
• Main outcomes and measures included estimated HRs of PFS for everolimus plus exemestane vs everolimus alone (primary objective) or capecitabine alone (key secondary objective).
• They assessed safety as a secondary objective.
• No planning for formal statistical comparisons was made.

Results

• Researchers enrolled a total of 309 postmenopausal women (median age, 61 years [range, 32-88 years]).
• The everolimus plus exemestane arm included 104 patients; the everolimus monotherapy arm included 103 patients; and the capecitabine monotherapy arm included 102 patients.
• From randomization to the analysis cutoff (June 1, 2017), median follow-up was 37.6 months.
• The investigators noted estimated HR of PFS of 0.74 for the primary objective of everolimus plus exemestane vs everolimus alone, and 1.26 for everolimus plus exemestane vs capecitabine alone.
• They noted potential informative censoring between treatment arms, and used a stratified multivariate Cox regression model to account for imbalances in baseline characteristics; they observed a consistent HR for everolimus plus exemestane vs everolimus, but closer HR to 1 for everolimus plus exemestane vs capecitabine.
• More frequent grade 3 to 4 adverse events were evident with capecitabine (74%; n=75) vs everolimus plus exemestane (70%; n=73) or everolimus alone (59%; n=61).
• Everolimus plus exemestane arm had serious adverse events more frequently (36%; n=37) than everolimus alone (29%; n=30) or capecitabine (29%; n=30) arm.