In the phase II PrE0102 trial reported in the Journal of Clinical Oncology by Kornblum et al, the addition of everolimus to fulvestrant (Faslodex) improved progression-free survival in postmenopausal women with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer resistant to aromatase inhibitor therapy.
In the double-blind trial, 131 women from 23 U.S. sites were randomized between May 2013 and November 2015 to receive fulvestrant at 500 mg on days 1 and 15 of cycle 1 and day 1 of cycle 2 and thereafter, plus either everolimus at 10 mg once daily (n = 66) or placebo (n = 65). The study was designed to have 90% power to detect a 70% improvement in median progression-free survival from 5.4 months to 9.2 months. Prophylactic corticosteroid mouth rinses were not used.
Median progression-free survival was 10.3 months in the everolimus group vs 5.1 months in the placebo group (hazard ratio = 0.61, P = .02), meeting the primary trial endpoint. Objective response rates were 18.2% vs 12.3% (P = .47). The clinical benefit rate was 63.6% vs 41.5% (P = .01). Median follow-up was 19.3 months among surviving patients. Median overall survival was 28.3 months in the everolimus group vs 31.4 months in the placebo group (HR = 1.31, P = .37).
Treatment-related adverse events of any grade were more common in the everolimus group, 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%). The most common grade ≥ 3 treatment-related adverse events in the everolimus group were oral mucositis (11% vs 0%), fatigue (6% vs 5%), and pneumonitis (6% vs 0%); no grade 4 events were observed in the everolimus group.
The investigators concluded, “Everolimus enhances the efficacy of fulvestrant in [aromatase inhibitor]–resistant, [estrogen receptor]–positive metastatic breast cancer.”
The study was supported by Novartis.
Noah Kornblum, MD, of Montefiore Medical Center, Albert Einstein College of Medicine, is the corresponding author for the Journal of Clinical Oncology article.
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