The I-SPY 2 TRIAL found that the neoadjuvant combination of trastuzumab emtansine (T-DM1) plus pertuzumab had greater benefit to HER2-positive breast cancer patients compared with paclitaxel plus trastuzumab, according to results presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, held April 16–20 in New Orleans.
The I-SPY 2 TRIAL is an adaptive trial design that aims to reduce costs, trial duration, and the number of patients that need to be tested in order to identify active drug combinations and the tumor types most likely to respond to treatment. The drugs are evaluated on an ongoing basis rather than having to design a new trial to test a particular drug or combination.
In this portion of the I-SPY 2 TRIAL, patients with invasive HER2-positive breast tumors 2.5 cm or larger were randomly assigned to either 12 cycles of T-DM1 plus pertuzumab, or to a control arm of paclitaxel plus trastuzumab. All patients then received 4 cycles of doxorubicin/cyclophosphamide followed by surgery.
Comparing rates of pathologic complete response (pCR) between patients in the experimental arm (n = 52) and patients in the control arm (n = 31), the researchers determined that there is a 90% to 94% chance that T-DM1 plus pertuzumab would show positive results in a phase III trial involving 300 patients with HER2-positive breast cancer.
The overall estimated pCR rate for all HER2-positive patients was 52% in the experimental arm compared with 22% in the control arm. The greatest benefit was for patients with HER2-positive, hormone receptor (HR)-negative disease where the estimated pCR rate was 64% compared with 33% in the control arm.
“These data provide a possible new treatment option for patients with newly diagnosed breast cancer that can not only effectively shrink the tumor in the breast but potentially reduce the chance of the cancer coming back later,” said study author Angela DeMichele, MD, MSCE, professor of medicine and epidemiology at the Perelman School of Medicine at the University of Pennsylvania, in a statement. “This also shows that by replacing older, non-targeted therapies with more effective, less-toxic new therapies, we have the potential to both improve outcomes and decrease side effects.”
A previous study of T-DM1 plus pertuzumab, the MARIANNE trial, demonstrated efficacy in treating metastatic HER2-positive disease, even though the combination did not produce better results than trastuzumab plus a taxane-based chemotherapy. “The fact that the MARIANNE study found this combination noninferior and less toxic was reassuring to us,” DeMichele told Cancer Network. The toxicity profile in the current trial was almost exactly the same as in the MARIANNE trial, noted DeMichele.
Trastuzumab plus pertuzumab and a taxane-based chemotherapy was also tested in I-SPY 2 and was found to be superior to paclitaxel plus trastuzumab. However, the trial was not designed to compared that regimen with T-DM1 plus pertuzumab.
The phase III KRISTINE clinical trial (NCT02131064) is currently ongoing, testing the combination of T-DM1 plus pertuzumab compared with docetaxel plus carboplatin, trastuzumab, and pertuzumab as a neoadjuvant therapy for women with HER2-positive breast cancer.