Two Experimental Breast-Cancer Drugs Pass Major Milestone in Study


Two experimental breast-cancer drugs passed a major milestone in a closely watched study that is part of a growing effort to revamp clinical trials and hasten the path of new medicines to the market.

Researchers reported Friday that one of the drugs, AbbVie Inc.‘s veliparib, proved especially promising against so-called triple negative breast cancer, an aggressive form of the disease for which there are few effective treatments.

Puma Biotechnology Inc. announced Dec. 3 its drug neratinib was similarly effective against a different form of breast cancer.

The initial successes help validate an experimental model intended to reduce a high rate of failure in cancer studies and possibly open a new path for the way the Food and Drug Administration approves some cancer drugs.

Both drugs were tested in an unconventional mid-stage trial called I-Spy 2. The trial involves patients with cancers confined to the breast, where a cure is possible but the disease is at high risk of spreading to other parts of the body. In one of the novel features of the study, the drugs were measured on their ability to eradicate the cancer in just six months, before any surgery to remove tumors.

Veliparib, for instance, when combined with the drug carboplatin and a six-month regimen of standard chemotherapy, achieved a complete response in 52% of patients compared with 26% for patients treated with standard chemo alone, according to Hope Rugo, an oncologist at University of California San Francisco who presented the findings Friday at the annual San Antonio Breast Cancer Symposium.

Typically, late-stage cancer drug studies succeed only 30% to 40% of the time, said Laura Esserman, director of the breast care center at University of California San Francisco and co-leader of I-Spy 2. Such trials can involve several thousand patients—many of whom wind up taking drugs that don’t help them—and can take nearly a decade to get an answer.

“Our goal is to improve the efficiency of trials and make it much easier for companies to develop and test drugs where they matter most,” Dr. Esserman said. “Our patients don’t have 10 years to figure out what the right treatments are.”

Five other compounds are currently in the trial and several others are being evaluated to participate.

Whether the promising results will translate into a speedier approval—or any approval at all—isn’t assured. A key to the I-Spy strategy is that the FDA accepts a complete response at six months—meaning that no residual cancer cells can be detected after the tumor and lymph nodes are removed—as a surrogate for a long-term benefit. The aim is for FDA to allow a drug on the market on that basis, on the condition that follow-up research demonstrates a long-term benefit.

“These are very provocative, interesting results,” Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said of the findings of the two drugs. But “there is uncertainty” whether such a response predicts the treatment will “prevent or delay the recurrence of breast cancer,” he said. “That’s the true clinical benefit.”

In most trials of patients whose cancer hasn’t spread beyond the breast, and in common medical practice, tumors are surgically removed before chemotherapy, after which doctors and patients wait months or years to see if the cancer comes back. Approval is based on that duration of benefit.

But earlier this year, the FDA granted so-called accelerated approval to Roche Holding‘s drug Perjeta for treating breast cancer in such patients, based on the complete responses achieved before surgery. Full approval is conditional on data from another trial confirming a long-term benefit.

Dr. Pazdur said weighing in Perjeta’s favor was that it was already approved for advanced breast cancer, and the agency had safety data on more than 5,000 patients. Also, the company had completed enrollment of patients in the confirmatory trial.

Further study will be required to validate a complete response as a predictor of long-term benefit for the new drugs and to provide assurance on safety, he said.

Partly to address the long-term issue, Dr. Esserman and her colleagues are launching a new trial called I-Spy 3, an international study in which they hope to enroll enough patients for each drug studied to test both the early complete response and the long-term follow up.

If a company going through such a process was able to file successfully with the FDA for accelerated approval, with a confirmatory trial well under way, “that should get agents to the market three to four years earlier,” Dr. Esserman said.

Puma Biotechnology Chief Executive Alan Auerbach said he plans to enter neratinib, which showed promise against a form of breast cancer known as Her2-positive, in the I-Spy 3 trial.

Scott Brun, vice president of pharmaceutical development for AbbVie, said the I-Spy 2 data will be “very important” to the company’s decision of how to proceed with development of its drug.

I-Spy 2 was launched in 2010 by the Biomarkers Consortium, reflecting use of and research into biological traits to help match participating patients with drugs with a greater chance of benefiting them. The consortium is a public-private partnership of the Foundation for the National Institutes of Health and includes the FDA, the National Institutes of Health and several pharmaceutical companies. The trial and I-Spy 3 are now sponsored by the nonprofit QuantumLeap Healthcare Collaborative, with funding from the Safeway Foundation, other philanthropic groups and pharmaceutical companies.

I-Spy 2 uses an adaptive trial design in which the experience of the early participants is used to channel later patients toward drugs showing evidence of effectiveness, a strategy researchers say helps more quickly identify drugs that are working and those that aren’t.