Kornblum N, et al. - Experts theorized that, in ER-positive metastatic breast cancer resistant to aromatase inhibitor (AI) therapy, everolimus plus the selective estrogen receptor (ER) downregulator fulvestrant would be more effective than fulvestrant alone. The effectiveness of fulvestrant in AI-resistant, ER-positive metastatic breast cancer was improved by everolimus.

Methods

• In this randomized, double-blind, placebo-controlled, phase II study, researchers included 131 postmenopausal women with ER-positive, human epidermal growth factor receptor 2-negative, AI-resistant metastatic breast cancer randomized to fulvestrant (500 mg days 1 and 15 of cycle 1, then day 1 of cycles 2 and beyond) plus everolimus or placebo.
• They designed this study to have 90% power to detect a 70% improvement in median progression-free survival (PFS) from 5.4 months to 9.2 months.
• Objective response and clinical benefit rate (response or stable disease for at least 24 weeks) were included in secondary end points.
• They did not use prophylactic corticosteroid mouth rinses.

Results

• Median PFS improved from 5.1 to 10.3 months (hazard ratio, 0.61 [95% CI, 0.40 to 0.92]; stratified log-rank P=.02) with the addition of everolimus to fulvestrant.
• Authors noted that objective response rates were similar (18.2% vs 12.3%;P=.47), but the clinical benefit rate was significantly higher in the everolimus arm (63.6% vs 41.5%; P=.01).
• Occurrence of adverse events of all grades were seen more often in the everolimus arm, including oral mucositis (53% vs 12%), fatigue (42% vs 22%), rash (38% vs 5%), anemia (31% vs .6%), diarrhea (23% vs 8%), hyperglycemia (19% vs 5%), hypertriglyceridemia (17% vs 3%), and pneumonitis (17% vs 0%), however grade 3 to 4 events were uncommon.