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I spy with my little eye …
BETHESDA, Md.—Aimed at improving the notoriously slow and expensive process of developing and approving new cancer drugs, the U.S. Food and Drug Administration (FDA) has released a regulatory guidance report describing a new way of conducting breast cancer drug trials that promises to significantly reduce the time and cost of getting new treatments to patients.
The newer, streamlined model, announced June 1, is based on a trial design tested in the I-SPY 2 Trial, an innovative Phase II breast cancer trial being conducted under the auspices of the Biomarkers Consortium, a public-private partnership led by the Foundation for the National Institutes of Health (FNIH), which includes the NIH, the FDA and multiple pharmaceutical companies and academic research centers.
Employing the latest advances in genetics, I-SPY 2 works by matching experimental drugs with the molecular makeup of tumors most likely to respond to them, according to the FDA. The design also tests multiple drugs at once, with the intent of getting the most effective ones into late-stage trials more quickly.
Historically, new cancer drugs have taken more than 10 years to be approved, at a cost of up to $1 billion and a 60- to 70-percent failure record in patients with late-stage cancer.
"Better options for patients with high-risk breast cancer are urgently needed," said Dr. Janet Woodcock, director of FDA's Center for Drug Evaluation and Research. "The FDA guidance explains how a promising drug identified in trials such as I-SPY 2 could be evaluated for FDA approval so patients could have rapid access if the drug proved better than current treatments. Predictability is the Holy Grail here—being able to identify promising drug candidates early and figuring out who they might work in."
Laura Esserman, director of the breast-care center at the University of California, San Francisco (UCSF) and co-leader of I-SPY 2, says, "We have 45,000 women dying each year of breast cancer. We should be compelled to move faster. Unless we do something different, people are going to give up on doing trials for cancer."
Kimberly O'Sullivan, communications officer for the FNIH, believes I-SPY and the new guidance could potentially cut the time it takes to test breast cancer drugs in half, due to several factors.
"It currently takes over a decade on average to develop a drug, about two- thirds of which time is spent in clinical testing of the drug," O'Sullivan tells ddn. "Breast cancer drugs can take a particularly long time to get to early-stage patients because they tend to be tested in patients with metastatic disease first, and are approved for use in early-stage patients only later, and after extensive additional trials."
The FDA's new guidance "establishes a pathway to test these drugs directly in high-risk, early-stage patients without having to be tested in metastatic disease first," O'Sullivan says. That's because the I-SPY Trial itself "is designed to screen new drugs after only six months of treatment, using an adaptive design that results in a drug being able to be 'graduated' as showing a high probability of efficacy in a smaller number of patients than in a typical Phase II trial.
"The result is less time plus less cost plus better targeted drugs for patients who really benefit from treatment," O'Sullivan adds.
I-SPY 2 also aims to collect information about experimental drugs that would then enable drug companies to design leaner, faster late-stage trials that enroll only patients whose tumors had a high probability of responding to the treatment.
"The vision is a 300-patient Phase III trial instead of a 3,000-patient trial, with better results," says Don Berry, head of Quantitative Sciences at MD Anderson Cancer Center in Houston and co-leader of the study.
Unlike conventional trials, in which no one sees results until the end, "we look at the data right away," Berry says. "What is learned in the early going helps to determine which drugs are assigned to patients later in the study, speeding the emergence of winners and losers."
Traditionally, surgery has been performed first, followed by chemotherapy and radiation, reflecting a long-standing preference to quickly remove tumors before beginning drug treatment.
In I-SPY 2, a patient's cancerous tumors are left in place for approximately six months, rather than being immediately removed surgically. Several new agents are tested in combination with standard chemotherapy in an effort to improve the chance of the tumor shrinking and completely disappearing—before surgery—in women with high-risk breast cancer. The trial is designed to learn which patients will have the most benefit from new targeted therapies to speed access under the FDA's new guidelines.
I-SPY 2, which also combines personalized medicine with a novel investigational design to identify women at high risk of early breast cancer recurrence, is underway at 19 major cancer research centers around the country.
"We are truly excited to see that the FDA is supportive of trials like I-SPY 2," Esserman says. "This really moves us much closer to getting the right drugs to the right patients at a time when they can be cured."