Adding everolimus to fulvestrant improves progression-free survival (PFS) among postmenopausal women with hormone-receptor positive (HR+), HER2-negative metastatic breast cancer, according to findings from the PrECOG 0102 (ClinicalTrials.gov Identifier: NCT01797120) study, presented at the 2016 San Antonio Breast Cancer Symposium.
The findings “provide additional evidence that adding everolimus to anti-estrogen therapy in AI resistant disease improves clinical outcomes,” reported Noah S. Kornblum, MD, of the Montefiore-Einstein Center for Cancer Care in the Bronx, New York.
The regimen was associated with increased toxicity, however, including more grade 3 events.
“The safety profile was consistent with everolimus in BOLERO-2,” Dr Kornblum noted.
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Dr Kornblum and colleagues hypothesized that combining everolimus and fulvestrant would be more effective than fulvestrant alone in AI-resistant breast cancer. They randomly assigned study participants to receive placebo plus everolimus or fulvestrant with everolimus. Patients were treated in an induction phase until evidence of disease progression or unacceptable toxicity for no more than 12 cycles (48 weeks), after which patients were unblinded to treatment and continued fulvestrant with or without everolimus.
Median PFS was 5.1 months with placebo vs 10.4 months with everolimus. Overall survival was similar between the study arms.
Additional study is needed to determine optimal sequencing of available agents and combinations in AI-resistant breast cancer, Dr Kornblum concluded.
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The most common grade 3 adverse events were stomatitis (affecting 9% of patients), pneumonitis (6%), fatigue (5%) and hyperglycemia (6%). Prophylactic corticosteroid mouthwash was not used in the study, but has been shown to reduce the risk of low-grade stomatitis.
- Kornblum NS, Manola J, Klein P, et al. PrECOG 0102: a randomized, double-blind phase II trial of fulvestrant plus everolimus or placebo in post-menopausal women with hormone-receptor positive, HER2-negative metastatic breast cancer. Paper presented at: 39th San Antonio Breast Cancer Symposium; December 2016; San Antonio, TX.