BETHESDA, Md.—Aimed at improving the notoriously slow andexpensive process of developing and approving new cancer drugs, the U.S. Foodand Drug Administration (FDA) has released a regulatory guidance reportdescribing a new way of conducting breast cancer drug trials that promises tosignificantly reduce the time and cost of getting new treatments to patients.
The newer, streamlined model, announced June 1, is based ona trial design tested in the I-SPY 2 Trial, an innovative Phase II breastcancer trial being conducted under the auspices of the Biomarkers Consortium, apublic-private partnership led by the Foundation for the National Institutes ofHealth (FNIH), which includes the NIH, the FDA and multiple pharmaceuticalcompanies and academic research centers.
Employing the latest advances in genetics, I-SPY 2 works bymatching experimental drugs with the molecular makeup of tumors most likely torespond to them, according to the FDA. The design also tests multiple drugs atonce, with the intent of getting the most effective ones into late-stage trialsmore quickly.
Historically, new cancer drugs have taken more than 10 yearsto be approved, at a cost of up to $1 billion and a 60- to 70-percent failurerecord in patients with late-stage cancer.
"Better options for patients with high-risk breast cancerare urgently needed," said Dr. Janet Woodcock, director of FDA's Center forDrug Evaluation and Research. "The FDA guidance explains how a promising drugidentified in trials such as I-SPY 2 could be evaluated for FDA approval sopatients could have rapid access if the drug proved better than currenttreatments. Predictability is the Holy Grail here—being able to identifypromising drug candidates early and figuring out who they might work in."
Laura Esserman, director of the breast-care center at theUniversity 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 compelledto move faster. Unless we do something different, people are going to give upon 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 totest breast cancer drugs in half, due to several factors.
"It currently takes over a decade on average to develop adrug, about two-thirds of which time is spent in clinical testing of the drug,"O'Sullivan tells ddn. "Breast cancerdrugs can take a particularly long time to get to early-stage patients because theytend to be tested in patients with metastatic disease first, and are approvedfor use in early-stage patients only later, and after extensive additionaltrials."
The FDA's new guidance "establishes a pathway to test thesedrugs directly in high-risk, early-stage patients without having to be testedin metastatic disease first," O'Sullivan says. That's because the I-SPY Trialitself "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' asshowing a high probability of efficacy in a smaller number of patients than ina typical Phase II trial.
"The result is less time plus less cost plus better targeteddrugs for patients who really benefit from treatment," O'Sullivan adds.
I-SPY 2 also aims to collect information about experimentaldrugs that would then enable drug companies to design leaner, faster late-stagetrials that enroll only patients whose tumors had a high probability ofresponding to the treatment.
"The vision is a 300-patient Phase III trial instead of a3,000-patient trial, with better results," says Don Berry, head of QuantitativeSciences at MD Anderson Cancer Center in Houston and co-leader of the study.
Unlike conventional trials, in which no one sees resultsuntil the end, "we look at the data right away," Berry says. "What is learnedin the early going helps to determine which drugs are assigned to patientslater in the study, speeding the emergence of winners and losers."
Traditionally, surgery has been performed first, followed bychemotherapy and radiation, reflecting a long-standing preference to quicklyremove tumors before beginning drug treatment.
In I-SPY 2, a patient's cancerous tumors are left in placefor approximately six months, rather than being immediately removed surgically.Several new agents are tested in combination with standard chemotherapy in aneffort to improve the chance of the tumor shrinking and completelydisappearing—before surgery—in women with high-risk breast cancer. The trial isdesigned to learn which patients will have the most benefit from new targetedtherapies to speed access under the FDA's new guidelines.
I-SPY 2, which also combines personalized medicine with anovel investigational design to identify women at high risk of early breastcancer recurrence, is underway at 19 major cancer research centers around thecountry.
"We are truly excited to see that the FDA is supportive oftrials like I-SPY 2," Esserman says. "This really moves us much closer to gettingthe right drugs to the right patients at a time when they can be cured."