The patients in the BOLERO-3 trial were randomized evenly to daily everolimus versus daily placebo, each added to weekly trastuzumab (Herceptin) and vinorelbine.
Everolimus is currently approved by the Food and Drug Administration for use in combination with exemestane to treat advanced hormone receptor–positive, HER2-positive breast cancer in postmenopausal women. It is also approved for selected indications in other cancers.
A fourth of patients had previously received lapatinib (Tykerb). The large majority had received one or two prior lines of therapy for metastatic disease.
Median progression-free survival was 1.22 months longer with everolimus (7.00 vs 5.78 months; hazard ratio, 0.78; P = .0067).
The overall rate of response did not differ significantly between the everolimus and placebo groups (41% vs. 37%).
The everolimus arm had higher rates than the placebo group for grade 3/4 stomatitis (13% vs. 1%), fatigue (12% vs. 4%), and hematologic adverse events. But the groups were statistically indistinguishable with respect to the time to definitive deterioration of global health status.
The rate of death was 36% with everolimus and 41% with placebo, a nonsignificant difference, although longer follow-up is needed for definitive overall survival data.
The trial was sponsored by Novartis, the maker of Afinitor. Dr. O’Regan disclosed that she is a consultant to Novartis, and receives research funding from Genentech, the maker of Kadcyla and Perjeta, and Novartis.