Traditionally, clinical trials have started with the sickest patients, those whose cancer has metastasized, which means it has spread from the breast to other parts of the body. The survival rate for these metastatic cancer patients is about 20 percent at five years, and at this stage, no treatment is likely to change the prognosis significantly. So the measure of success in these trials is not a cure or survival but extending a patient’s life by a few extra—very precious—weeks or months. If the drug being tested does prove to extend life for these patients, it must be re-tested on early stage patients whose lives might be saved. This stage of testing could take many years more.
I-Spy-2 patients have biologically high-risk tumors—minimum size is 2.5 cm—but their cancer has not metastasized. “If the goal is to make sure people don’t die of this disease, you want to make sure you’re giving these agents at a time when you might be able to cure someone and improve their care,” Esserman says. “Our subjects are people at the highest risk who are most in need of having their outcomes improved.”
Putting Drug Treatment First
In I-Spy-2, drug treatment comes before surgery. In some ways, the current treatments are backwards if your goal is to stop the cancer from spreading. After all, metastatic disease is the real killer, and surgery isn’t very useful in stopping it. “Once the microscopic cells have sloughed off from the lesion in your breast and begun their migration to another organ, like the liver or the lung, it doesn’t matter what operation I do, it’s not going to save your life,” Esserman says. “What saves your life is if you happen to be the person whose migrating tumor cells will be destroyed by the drug therapies we have.” Not all drugs are equally effective on all cancers, and if you operate and take the tumor out, you don’t have any way to tell if the drug is working, except if the cancer does spread or recurs. Give the drugs first and you can monitor the tumor itself. “We’ve known for some time that scheduling surgery before or after chemo does not affect long-term outcomes,” Dr. Esserman says. “By holding off on the surgery, we can determine if the drug is having an effect on the tumor itself. We don’t have to wait years to see if the cancer returns to learn if the drug was effective.”
“Maybe some day, we’ll evaluate a tumor based on an array of 500 genes and every patient will be given a specific pill that will deliver just the right amount of the exact drug based on her biomarkers,” Berry says. “We’re not trying to do that with I-Spy-2, and obviously it’s enormously difficult, but we’re moving in that direction.”
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