Liz Meszaros, MDLinx | August 09, 2017
Adding pembrolizumab to standard therapy before surgery in patients with locally advanced triple-negative breast cancer (TNBC) or hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer improved pathological complete response (pCR) rates, according to results from the Investigation of Serial Studies to Predict Your Therapeutic Response and Imaging And molecular Analysis 2 (I-SPY 2 TRIAL). Results were presented at the annual American Society of Clinical Oncology 2017 meeting.
“We found that pembrolizumab essentially more than tripled the rate of pathologic complete responses in HER2- patients in the I-SPY 2 TRIAL,” said Andres Forero, MD, professor, division of hematology and oncology, and head of the breast cancer program, at University of Alabama at Birmingham.
The I-SPY 2 trial is a multicenter, phase 2, platform trial to assess novel neoadjuvant therapies, with a primary endpoint of pCR. It represents a collaborative effort among academic investigators from 20 major cancer research centers across the United States and Quantum Leap Healthcare Collaborative, the US FDA, and the Foundation for the National Institutes of Health Cancer Biomarkers Consortium, pharmaceutical and biotech companies, and patient advocates.
To determine individual treatment plans, researchers used breast MRI scans, breast core biopsies, and serum samples. In addition, chemotherapy treatment before surgery was included, with the possibility of an investigational drug as part of treatment.
Dr. Forero and fellow researchers randomized patients with invasive BC ≥ 2.5 cm via exam, or ≥ 2 cm via imaging. Subjects were treated with weekly paclitaxel for 12 doses (control plus or minus an experimental agent), followed by doxorubicin/cyclophosphamide for four doses.
In all, 69 patients were randomized to pembrolizumab. In 29 patients with TNBC, raw pCR rates were increased by more than 50%, and estimated pCR rates by 40%. In 40 HR+/HER- patients, these rates increased by 13% and 21%, respectively.
Immune-related grade 3 adverse events were seen in five patients, one with hypophysitis and four with adrenal insufficiency. Seven patients had grade 1-2 thyroid abnormalities.
“Not all breast cancers are the same, and there has continued to be a significant gap in the treatment options available for patients with certain subtypes, particularly TNBC,” said Dr. Forero, who is also a senior scientist, UAB Comprehensive Cancer Center. “The results observed in this trial not only are encouraging, but set the stage for a shift in treatment toward combinations that can make a difference in patient outcomes.”
He concluded: “The bottom line is that the results of this trial can help make investigational drugs available to more women in the future. We are hopeful that there will be new and better options available to our patients right at diagnosis.”