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New Drug Combo Delays Disease Progression in Advanced Breast Cancer

Bortezomib/fulvestrant shows promise in mid-stage trial

A new combination of cancer drugs delayed disease progression in patients with hormone receptor (HR)-positive metastatic breast cancer, according to results from a randomized phase II trial from Yale University. The findings were presented at the 2014 San Antonio Breast Cancer Symposium, held December 6­–9.

The study enrolled 118 post-menopausal women with metastatic HR-positive breast cancer whose disease continued to progress after being treated with an aromatase inhibitor. The trial found that the combination of bortezomib (Velcade, Millennium/Takeda) and fulvestrant (Faslodex, AstraZeneca) doubled the rate of survival at 12 months and reduced the chance of cancer progression overall compared with fulvestrant alone.

Bortezomib is a proteasome inhibitor that prevents cancer cells from clearing toxic material. It is usually used to treat multiple myeloma. Fulvestrant causes clumping of the estrogen-receptor protein. When bortezomib blocks the ability of the cell to clear these protein clumps, they grow larger and become toxic to the cancer cells. This, in turn, amplifies the efficacy of fulvestrant, a drug commonly used in breast cancer patients.

The drug combination doubled the number of patients whose cancer had not progressed after 1 year from 14% to 28%, according to lead investigator Dr. Kerin Adelson.

“This provides the foundation for future studies combining selective estrogen-receptor destroyers with proteasome inhibitors,” Adelson said. “Because the study showed a statistically significant benefit among patients whose disease progressed on an aromatase inhibitor, a larger phase III study comparing this combination to other approved therapies used after initial therapies fail, like exemestane and everolimus, should be done.”

The study results also suggest that the drug combination can delay or overcome resistance to fulvestrant, Adelson said. The combination should be studied in other populations of patients, he added, including those who are newly diagnosed with metastatic breast cancer and those who have already progressed on fulvestrant.

Source: Yale University; December 10, 2014.


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