A new guidance document issued this week by the U.S. Food and Drug Administration will allow drug companies to test their medications for a few months on women with highly aggressive breast cancers before they have surgery, instead of waiting until the drug has been proven first in gravely ill patients.

"We're looking at introducing drugs into a very early stage of breast cancer, where a patient has a primary tumor and the chemotherapy is given before surgery," Dr. Richard Pazdur, director of the FDA's cancer drug office, said in an interview at the American Society of Clinical Oncology meeting in Chicago.

"The aim of this therapy would be to cure the woman of breast cancer," Pazdur said. "It's moving a very promising drug into a early stage of the disease with a curative intent."

If a drug succeeds in eradicating the cancer to the point where there is no sign of it in the breast or lymph nodes - something called pathologic complete response - companies could win accelerated approval.

That represents a significant change from the current approach, in which promising drugs only are tested in earlier stage cancers after they have first proven to be safe and effective in advanced, metastatic cancer.

"If you are a patient with early stage breast cancer and you hear about a great new drug for metastatic breast cancer, it's probably not going to be available to you under the current model for a decade," said Dr. Tatiana Prowell, a cancer specialist at Johns Hopkins in Baltimore and a medical officer for the FDA.

Prowell and Pazdur wrote about the guidelines in the current New England Journal of Medicine.

PART OF PUSH AT FDA

The change is part of a push at the FDA to spur innovation and get more effective drugs to the patients who need them.

"We really do want to be very forward-leading," FDA Commissioner Dr. Margaret Hamburg said in a briefing with Reuters on Thursday.

"We understand the importance of taking an advance in science as quickly as we can to the patients who need them, always being mindful of our responsibility of looking at the issues of safety and efficacy."

FDA is taking a risk with the new strategy, which will expose women with much earlier-stage disease to potential safety issues of new medications.

Traditionally, by the time new drugs are tried on women with earlier-stage disease they have been tested in thousands of women with much more advanced disease, for whom the risk of trying the drug is balanced with its potential for prolonging their lives.

To help mitigate these risks, the new guidance document will apply to women with an especially deadly form of breast cancer called triple-negative breast cancers.

Most breast tumors are called estrogen-receptor positive, because they are fueled by the hormone estrogen. About 20 percent are HER2-positive, because a protein called HER2 is involved. A third type is driven by the hormone progesterone.

These types of cancer have good treatments.

Then there are basal-like or triple-negative tumors, so named because they lack estrogen, progesterone or HER2 receptors needed for most breast cancer drugs to work.

Triple-negative breast cancers tend to grow and spread more quickly than most other types of breast cancer, and they occur more often in younger women and in African-American women.

"NOT FOR EVERY PATIENT"

"This is not for every patient. It should be for patients that are most likely to benefit and also those that are at highest risk of having a recurrence of the disease," Pazdur said.

Trials would be structured so that women are treated with either chemotherapy or chemotherapy plus an experimental drug for a few months prior to surgery.

If no sign of the cancer is found during surgery, the woman has achieved a complete pathological response. Researchers would then compare response rates in the two groups, and if the drug has helped cure significantly more cancers, it would be given a provisional type of approval called accelerated approval.

Drug companies would continue to follow women for several years to see if their cancers come back, and if women continue to be disease-free, companies could get full approval for the treatment. FDA is accepting comments about its draft plan through the end of July.

Reaction so far has been positive.

"We clearly need new approaches to getting stuff to the early-disease setting," said Dr. George Sledge, co-director of breast cancer program at the Indiana University Simon Cancer Center and immediate past president of ASCO.

FASTER ACCESS TO NEW DRUGS?

He said the new approach is not a perfect solution to the problem, but it's a good first step.

"It recognizes that we want to try to move drugs up front into an early disease setting as soon as possible - not wait until the patient is beat up and out of chances and out of hope before we throw a drug at the patient and hope it does something."

Leerink Swann analyst Howard Liang said the new approach could potentially speed access to several breast cancer drugs in development, including treatments by Roche, GlaxoSmithKline , Celgene Corp, Onyx Pharmaceuticals, Bayer, Boehringer Ingelheim, Eli Lilly and Co, Eisai Co Ltd and Puma Biotechnology Inc.

FDA is basing much of its plan on a clinical trial known as I-SPY 2, a Phase II breast cancer trial being conducted by the Biomarkers Consortium, a public-private partnership run through the Foundation for the National Institutes of Health.

The trial, being run by Dr. Laura Esserman at the University of California at San Francisco and Dr. Donald Berry of MD Anderson Cancer Center in Houston, relies on specific genetic signatures or biomarkers in tumors to select those who might benefit from testing with this new approach.

The trial uses an approach called adaptive design, in which researchers continuously monitor which patients are responding to drugs and try to give drugs to those most likely to respond.

"If a therapy is doing well in a particular subset of patients, it gets a higher probability of being assigned to a patient in that subset," Berry said.

The design allows the team to test new treatments with far fewer participants and in half the normal time, cutting back on the costs of developing treatments.

Hamburg said she is meeting with the board at the ASCO cancer meeting this week to discuss this and other approaches to innovative clinical trial design.

"We feel more powerfully than ever before that how the studies are structured from the get-go really matters for our ability to do our job in an effective and efficient manner," she said.

"We really do want to be part of the scientific discussions early on to help shape how research is done."

Breast cancer is the second-leading cause of cancer death in women, exceeded only by lung cancer, according to the American Cancer Society.

(Editing by Eric Walsh)

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