Treating Advanced Breast Cancer in Community Settings - Episode 11
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Several second-line treatment options exist for patients with ER-positive metastatic breast cancer following progression on frontline therapy. The question facing many treating physicians is whether to use an aromatase inhibitor, tamoxifen, exemestane, or everolimus plus exemestane, notes Adam M. Brufsky, MD, PhD.
The combination of everolimus and exemestane is best utilized as a second-line therapy, believes Hope S. Rugo, MD. In this setting, patients are in better shape and there is less disease burden. In the pivotal BOLERO-2 trial, patients had progressed on at least one prior therapy, with many treated in the second-line setting. Prior therapies included letrozole or anastrozole (100%), chemotherapy (68%), tamoxifen (48%), and fulvestrant (16%).
In the BOLERO-2 trial, progression-free survival (PFS) was significantly extended for patients with HER2-negative, ER-positive metastatic breast cancer who received treatment with everolimus plus exemestane versus exemestane alone. The median PFS by investigator assessment was 7.8 months with everolimus compared with 3.2 months with exemestane alone (HR = 0.45; P <.0001). The objective response rate was 12.6% in the everolimus arm versus 1.7% with exemestane alone.
It is common in the community setting to think of everolimus plus exemestane as a later-line therapy; however, the combination seems most effective in the second-line setting, Rugo believes. The combination does seem to have the greatest efficacy in earlier settings, when patients are better able to tolerate the side effects, agrees Dialecti Voudouris, MD.
The FDA recommended starting dose for everolimus is 10 mg once daily with or without food. In some situations, the initial dose is reduced and then titrated back to 10 mg, to avoid side effects. However, with ample familiarity with the drug and proper education for support staff, this initial dose reduction can be avoided and treatment can be continued for a longer duration, Voudouris suggests.