Two Drugs Appear to Delay Progression of Breast Cancer

Both drugs, pertuzumab from Genentech and everolimus from Novartis, also showed signs in clinical trials that they could prolong lives, though researchers said it was too early to say that definitively.

Results of the studies, which were sponsored by the companies, are being presented this week at the San Antonio Breast Cancer Symposium and were published online Wednesday in The New England Journal of Medicine.

Pertuzumab is designed to complement Genentech’s big-selling drug Herceptin for the roughly 20 percent of breast cancer patients whose tumors have elevated levels of a protein called Her2. Both pertuzumab and Herceptin block the action of the protein but in different ways.

In a late-stage clinical trial involving 808 patients, women randomly chosen to receive pertuzumab, Herceptin and the chemotherapy drug docetaxel went a median of 18.5 months before their tumors worsened or they died, a measure known as progression-free survival. That was significantly longer than the 12.4 months for those who received a placebo, Herceptin and docetaxel.

“We have an improvement in progression-free survival that is six months,” Dr. José Baselga, chief of hematology and oncology at Massachusetts General Hospital, said in an interview. “That’s huge. By any criteria we want to analyze, this is clinically meaningful.”

Dr. Baselga was a principal investigator in the studies of both pertuzumab and everolimus and has been a paid consultant for Genentech and Novartis.

He said the addition of pertuzumab did not increase cardiac dysfunction, a worrisome side effect of Herceptin.

Genentech and its parent company, Roche, have applied in the last few days for permission to market pertuzumab in the United States and Europe.

Approval could help the company recover from the recent decision of the Food and Drug Administration to revoke the approval of another Genentech drug, Avastin, for the treatment of breast cancer.

Avastin had been approved based on a trial that showed it delayed the worsening of tumors by 5.5 months — almost as big a gain as seen now with pertuzumab. But the use of Avastin did not prolong lives, and subsequent studies found a much smaller improvement in progression-free survival.

That could make the F.D.A reluctant to approve pertuzumab unless it also helps women live longer. But Dr. Sandra J. Horning, head of cancer clinical trials at Genentech, said the pertuzumab results on tumor progression were more trustworthy than the original Avastin results because the trial was conducted more carefully.

Novartis’s drug, everolimus, is a tablet that is already sold under the name Afinitor to treat kidney cancer and some rare tumors. Novartis plans to apply for the tablet’s approval as a breast cancer treatment by the end of the year.

Its clinical trial involved 724 postmenopausal women with hormone receptor-positive metastatic breast cancer.

The women who took both everolimus and a drug called exemestane had a median progression-free survival of 7.4 months compared with 3.2 months for those who took a placebo plus exemestane. Exemestane, also known by the brand name Aromasin, deprives tumors of estrogen, which can fuel their growth.

Women in the study already had failed to benefit from other estrogen-depriving drugs. So perhaps it is not surprising that the control arm did not do that well on exemestane alone.

“They put it up against a weak opponent,” said Dr. Peter Ravdin, a breast cancer specialist at the University of Texas Health Science Center at San Antonio, who was not involved in the study.

But trial investigators said the comparison was valid because in daily practice, doctors often use exemestane when other estrogen-blocking drugs fail.

Everolimus works by inhibiting mTOR, a protein that often spurs tumor growth after tumors become resistant to hormone therapy.

“This is the first time we have a strategy to revert endocrine resistance, which has been the holy grail of therapy for endocrine-positive tumors,” Dr. Baselga said.

Another drug — entinostat, from privately held Syndax Pharmaceuticals — might also be able to do that, according to the results of a small study presented in San Antonio. Women who received that drug plus exemestane had delayed tumor progression and also lived months longer than those who took exemestane alone.

Those results will have to be confirmed in a larger trial, and it will be several years before entinostat can reach the market.

Everolimus costs about $7,000 a month when used for kidney cancer. The drug can have significant, even fatal, side effects like mouth sores, infections and lung inflammation. That could give some doctors pause about adding it to hormone therapy.

“Hormone therapy, which is relatively well tolerated, becomes closer to chemotherapy” in terms of side effects, said Dr. Clifford A. Hudis, chief of the breast cancer medicine service at the Memorial Sloan-Kettering Cancer Center, who was not involved in the study.

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