Larger Everolimus Trials Needed for Breast Cancer Subpopulations

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(ChemotherapyAdvisor) – Improved patient selection is needed to assess everolimus for advanced breast cancer among patient subpopulations other than those with ER+ tumors, indicates a systematic review of data from 28 studies of this and several other inhibitors of mammalian target of rapamycin (mTOR). The analysis was published in Gynecologic Oncology

The Breast Cancer Trials of Oral Everolimus-2 (BOLERO-2) study marked “a turning point in the evaluation of everolimus in the treatment of estrogen receptor-positive breast cancer,” the authors emphasized.

“PI3K/AKT/mTOR pathway is a crucial mediator of tumor progression,” lead author Flora Zagouri, MD, PhD, of the Comprehensive Cancer Center, Vienna, Austria wrote. “Everolimus, an mTOR inhibitor, is the most promising agent of this category given the positive results of The Breast Cancer Trials of Oral Everolimus-2 (BOLERO-2) study.”

But large clinical trials are still needed to assess the drug's potential among women diagnosed with triple-negative breast cancer, the authors concluded. Overall, published studies of everolimus in metastatic and neoadjuvant settings did not involve “well-characterized specific cancer subpopulations,” the authors cautioned; five everolimus monotherapy trials for metastatic breast cancer suggested “only modest activity.”

However, improved patient selection may yet establish benefits for specific patient subpopulations, the authors noted.

The PI3K/AKT/mTOR pathway is involved in cellular metabolism, proliferation, growth and survival, and accumulating evidence indicates genetic and epigenetic dysregulation of this pathway is involved in tumorigenesis, the authors noted. High levels of phosphrylated, activated mTOR, Akt, and 4E-BP1 are associated with nodal metastasis and poor disease-free survival.

The systematic review of mTOR inhibitor therapies for breast cancer included data for 1,492 patients who received everolimus (from 15 early-phase clinical trials and one phase III study), as well as 1,245 patients with metastatic or refractory breast cancer who were administered temsirolimus (from 8 papers, including 1 phase III study). A single phase II study of sirolimus (representing 400 patients with metastatic breast cancer) was included, and 2 early-phase trials for MKC-1 among patients with metastatic or recurring breast cancer, were included.

Everolimus is marketed as Afinitor by Novartis. The authors did not report any conflicts of interest.

Abstract

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