Kathy D. Miller, MD; Hope Rugo, MD


December 20, 2013

In This Article

I-SPY, a Novel Trial Design

Dr. Miller: That is not the end of the platinum DNA-damaging agent story here. The I-SPY group that you have been part of has looked at those issues in one of their studies as well. This is one of the first I-SPY arms that had results.

Dr. Rugo: It is the first to have results presented publically. There was a press release last week about the second arm to graduate from the I-SPY 2 trial, which was neratinib, the oral tyrosine kinase inhibitor. The trial that I was co-chaperone of within I-SPY 2[7] with Funmi Olopade is quite intriguing. I'll make a brief mention about I-SPY 2, because it's a complicated but exciting novel trial design.

I-SPY 2 is designed as a fluid trial. It's an adaptive randomization. There is a standard arm: paclitaxel for 12 weeks, followed by doxorubicin and cyclophosphamide every 2-3 weeks for 4 doses, followed by surgery. Patients are then randomly assigned to the control arm or the control arm with a series of novel agents or regimens added to paclitaxel. So, it's a fluid trial in that you can add and drop drugs as you learn. Another novel part of the trial is that patients were selected to have a better chance to benefit from chemotherapy. Patients were eligible for the trial if they had MammaPrint high-risk disease, or if they had triple-negative or HER2-positive breast cancer, even if their MammaPrint was low-risk, which was a small number of patients. Patients who had ER-positive low risk by MammaPrint didn't go on the trial, because they were least likely to benefit.

Dr. Miller: That makes sense. One could argue that perhaps those patients shouldn't be treated with chemotherapy before or after surgery.

Dr. Rugo: No genomic study is going to be perfect. There may be some patients who benefit from chemotherapy.

Dr. Miller: It's a reasonable enrichment to look at pCR as a readout of efficacy.

Dr. Rugo: It avoids the problem of treating patients who don't need chemotherapy. That is the eligibility. The second and probably most complicated part of this trial is the adaptive randomization. This plan is the brainchild of Don Berry, the well-known statistician. The trial itself was designed and came about through a lot of collaborations with Laura Esserman and the Foundation of the National Institute of Health's Biomarker Consortium, and was funded by a number of different places, including the Safeway Foundation and some other philanthropic organizations. And then pharmaceutical companies gave money to the trial (but not to their drug).


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