Combination Therapy May Help Some Patients with Advanced Breast Cancer
A combination of two available cancer drugs could offer a new treatment option for postmenopausal women whose advanced breast cancer has stopped responding to hormonal therapy, researchers said last week at a scientific meeting in Stockholm, Sweden.
The experimental treatment is a combination of everolimus (Afinitor) and exemestane. In a phase III clinical trial, women who received the combination lived for a median of 11 months without the disease progressing, compared with about 4 months for women who received exemestane alone.
"The benefit is quite remarkable," said lead investigator Dr. José Baselga of the Massachusetts General Hospital, who presented the findings at the European Multidisciplinary Cancer Congress. Many patients in the trial had already received multiple therapies, he noted.
In the United States, everolimus is approved for treating advanced kidney cancer and a form of pancreatic cancer. The drug inhibits a protein called mTOR, which participates in a signaling pathway that is highly active in many cancer cells and promotes cell growth and proliferation. Exemestane, an aromatase inhibitor, is used to treat metastatic breast cancer and may be effective when other aromatase inhibitors no longer work.
The combination of these drugs, Dr. Baselga noted at the European meeting, represents a new potential therapeutic option for these women. The study is "probably the most positive trial ever in metastatic estrogen receptor (ER)-positive disease," he said in a video interview.
"These are impressive results," commented Dr. Jo Anne Zujewski, head of Breast Cancer Therapeutics in NCI's Division of Cancer Treatment and Diagnosis, who was not involved in the research.
Although there are no data on overall survival yet, Dr. Zujewski agreed that the combination therapy is a new potential option for some patients. The side effects were generally manageable, she added.
The trial included 724 patients from 24 countries. All of the participants had received the aromatase inhibitors letrozole or anastrozole, nearly half had received tamoxifen, and two-thirds had received chemotherapy.
Novartis, the trial's sponsor, plans to seek regulatory approval this year for everolimus in treating ER-positive advanced breast cancer.
"I would be very surprised if this drug were not approved [for the new indication]," said Dr. Ruth O'Regan, director of the Translational Breast Cancer Research Program at Emory University's Winship Cancer Institute, who also had no role in the trial.
She views the combination therapy as a potential alternative to chemotherapy for treating ER-positive advanced breast cancer when hormonal therapies have stopped working.
When resistance to hormonal therapies occurs, Dr. O'Regan explained, additional signaling pathways become activated. Unlike chemotherapy, which targets rapidly dividing cells, mTOR inhibitors are an example of the kind of treatment that may block growth-promoting signaling pathways.
Many lab studies have suggested the promise of this approach. "What's nice about the current study is that we now have confirmation that this strategy works from a study in patients," said Dr. O'Regan, who has led clinical trials of everolimus.
The results add to recent findings on everolimus and breast cancer. Last December at the San Antonio Breast Cancer Symposium, for instance, researchers presented positive results from a trial of everolimus plus tamoxifen for ER-positive, HER2-negative, metastatic disease.
And in 2009, Dr. Baselga and his colleagues reported that the addition of everolimus to letrozole benefited patients with newly diagnosed ER-positive breast cancer as compared with letrozole alone.
The next step is to "digest the data," Dr. Baselga said in Stockholm. "But it would seem to me that mTOR inhibition will play a major role in all disease stages of ER-positive breast cancer."