Lisa A. Carey, MD
While recent findings from the I-SPY 2 trial have shown potential with the combination of ado-trastuzumab emtansine (T-DM1; Kadcyla) and pertuzumab (Perjeta) for patients with HER2-positive breast cancer, the neoadjuvant space still has a lot of work ahead, according to Lisa A. Carey, MD.
, who is the medical director of the University of North Carolina Breast Center and chief of Hematology/Oncology and physician-in-chief of the North Carolina Cancer Hospital, comments on the recent I-SPY 2 and KRISTINE findings, the I-SPY 2 program as a whole, and the work ahead in the neoadjuvant landscape of HER2-positive breast cancer.
OncLive: What are your thoughts on the I-SPY 2 trial of T-DM1/pertuzumab versus paclitaxel/trastuzumab in the neoadjuvant setting?
: In this particular trial, the control arm received trastuzumab and paclitaxel for 12 weeks, then they got AC (doxorubicin and cyclophosphamide), and then they went to surgery. In the investigational arm, patients received T-DM1 and pertuzumab, so they switched out 2 drugs. There is a hidden chemotherapy kind of tucked inside T-DM1.
That said, this clearly is a positive trial. What they have is a difference that is based on their statistical assumptions—that T-DM1/pertuzumab would outperform paclitaxel/trastuzumab. I’m a little worried about the underperformance of the control arm, which only has 30 patients in it.
What did the KRISTINE study show in regard to T-DM1?
The KRISTINE study is a randomized neoadjuvant clinical trial comparing TCHP with T-DM1/pertuzumab in HER2-positive breast cancer—very similar to the I-SPY 2 trial. They received it for 6 cycles. In that setting, TCHP outperformed T-DM1/pertuzumab in pCR significantly more than 10%.
On the other hand, while the pCR rate was in favor of the TCHP arm, toxicity was in favor of the T-DM1/pertuzumab arm, with serious adverse events at approximately 5% [versus] almost 30% in the TCHP arm.
There is going to have to be some thoughtful consideration of how T-DM1 plus pertuzumab moves forward, given a pretty good-sized study that used TCHP where it was a significantly lower pCR rate.
Can you explain the purpose of the I-SPY 2 program?
Basically, it is a framework for trying to identify promising drugs or regimens but it is a very statistically complicated framework. Essentially, the trials are mostly made of up clinical subsets by estrogen receptor, progesterone receptor, and HER2 receptor [status]. Low MammaPrint-score luminal tumors are excluded, so some of the low biologically risk tumors are not selected.
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