Combining two drugs in post-menopausal women with a certain type of advanced breast cancer more than doubled the time they lived without their disease getting worse, a new study data showed.
The clinical trial results showed that women treated with a combination of Novartis AG’s Afinitor or everolimus, and Pfizer's estrogen-blocker Aromasin, known generically as exemestane, had progression-free survival (PFS) of as much as seven months more than women treated with the Pfizer drug alone.
Jose Baselga of Massachusetts General Hospital and Harvard Medical School, who led the trial and presented the data at the European Multidisciplinary Cancer Congress (EMCC) in Stockholm said, “This is a highly significant improvement in the time to disease progression. It's quite remarkable.” He said side effects were consistent with those previously reported in trials of Afinitor and did not lead to a worse quality of life for patients on the drug. The most common severe side effects of Afinitor were mouth ulcers, anemia and shortness of breath.
Baselga's analysis of the data showed that PFS for women in the Afinitor group was 6.9 months versus 2.8 months for those not taking the Novartis drug - a 57 percent improvement. The trial was stopped early after a separate independent analysis by a central review committee showed that Afinitor extended PFS to 10.6 months compared to 4.1 months - a 64 percent improvement.
“These results are impressive and, potentially, could represent a new therapeutic option,” Baselga said.
Afinitor targets mTOR, a protein that acts as an important regulator of tumor cell division, blood vessel growth and cell metabolism. It is already approved for other types of cancer, such as kidney and a rare type of pancreatic cancer.
Herve Hoppenot, president of Novartis's oncology division, said the magnitude of benefit seen in this trial showed that Afinitor is “a potential important new treatment approach”. The Swiss drug maker is planning to file for regulatory approval of Afinitor in breast cancer by the end of this year.
The hormone estrogen promotes the growth of about two thirds of breast cancers, and hormonal therapies such as Aromasin which block the effect of estrogen or reduce its levels are used to treat these so-called hormone receptor-positive breast cancers. But many breast cancer patients, and nearly all those with advanced forms of the disease where it has spread to other parts of the body, become resistant to hormonal therapy.
“When patients stop responding to hormonal therapy, the benefits from any secondary therapy are limited,” Baselga said. The Phase III clinical trial, known as BOLERO 2, was designed to test the efficacy of Afinitor in patients resistant to aromatase inhibitors - drugs that cut the amount of estrogen produced and help to slow or reverse the growth of the cancer.
It was as conducted in 24 countries in 724 patients with an average age of 62. All patients had already been treated with the aromatase inhibitors anastrozole, sold by AstraZeneca as Arimidex, or the generic drug letrozole. Some had also been treated with tamoxifen, fulvestrant and chemotherapy.