FDA Approves Everolimus for Advanced Breast Cancer

The FDA has approved everolimus (Afinitor, Novartis) for treating patients with hormone receptor-positive, HER2-negative breast cancer, when given in combination with the aromatase inhibitor exemestane.

Everolimus is a mammalian target of rapamycin (mTOR) inhibitor that has been shown to significantly increase progression-free survival (PFS) in patients with this particular genetic subtype of advanced breast cancer. While the drug has already received prior approvals for renal cell carcinoma, progressive neuroendocrine tumors of pancreatic origin (PNET), and subependymal giant cell astrocytoma, a type of brain tumor associated with tuberous sclerosis, this is its first indication for breast cancer.

“This is the first approval from the class of drugs known as mTOR inhibitors for the treatment of postmenopausal women with advanced hormone-receptor positive breast cancer,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a statement. “Afinitor is another example of the value of continuing to study drugs in additional types of cancer after their initial approval.”

The approval of everolimus for breast cancer was based largely on the results of the BOLERO-2 trial, which were published in The New England Journal of Medicine in February. The randomized phase III trial compared everolimus and exemestane with a placebo and exemestane in 724 patients who had hormone receptor-positive advanced breast cancer and who had recurrence or progression while receiving previous therapy with a nonsteroidal aromatase inhibitor in the adjuvant setting or to treat advanced disease, or a combination of both.

José Baselga, MD, PhD

The interim analysis of the study by local investigators found that median PFS in the everolimus plus exemestane arm was 6.9 months compared with 2.8 months in the placebo plus exemestane arm (hazard ratio [HR]=0.43; CI 95%, 0.35-0.54; P <.001). A separate central assessment also found that median PFS was 10.6 months in the everolimus arm and 4.1 months in the control arm (HR=0.36; 95% CI, 0.27-0.47; P < .001).

“I think everolimus is going to be a major addition to therapy,” said José Baselga, MD, PhD, a professor in the Department of Medicine at Harvard Medical School and chief of Hematology/Oncology at Massachusetts General Hospital, who also served as lead author of the BOLERO-2 study, in a previous interview. “In the patient population that was part of the BOLERO-2 study, the addition of everolimus had very meaningful clinical improvement for patients. I would think that everolimus will become a standard of care in that indication.”