Results from a nationwide clinical trial, conducted in part at the University of Alabama at Birmingham, has found that adding the drug pembrolizumab in combination with standard therapy before surgery shows potential for meaningful outcomes in patients with locally advanced triple negative (TNBC) or hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancers.
The findings from I-SPY 2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis 2) were exclusively presented at the annual meeting of the American Society of Clinical Oncology last week.
I-SPY 2 is a clinical trial for women with newly diagnosed, locally advanced breast cancer. It is testing whether adding investigational drugs to standard chemotherapy, based on molecular tests to identify the best drug for each patient’s individual tumor type, is better than standard chemotherapy alone before having surgery.
“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, M.D., professor in the UAB Division of Hematology and Oncology, and head of the breast cancer program at UAB.
The I-SPY 2 TRIAL is a collaborative effort among academic investigators from 20 major cancer research centers across the United States and Quantum Leap Healthcare Collaborative, the U.S. Food and Drug Administration, and the Foundation for the National Institutes of Health Cancer Biomarkers Consortium, pharmaceutical and biotech companies, and patient advocates.
UAB, Alabama’s leader in personalized medicine, has actively enrolled about 150 patients in the last five years.
The I-SPY 2 TRIAL is testing the idea of tailoring treatment by using molecular tests to help identify which patients should be treated with investigational drugs. The treatment phase of the trial consists of testing multiple investigational drugs that are thought to best match the biology of each participant’s tumor. Information from each participant who completes the study treatment is also used to help decide treatment for future women who join the trial. This allows study researchers to learn more quickly which investigational drugs will be most beneficial for women with certain tumor characteristics.
In order to determine individual treatment plans, the study includes procedures such as breast MRI scans, breast core biopsies and research blood draws. It also includes chemotherapy treatment before surgery, and the possibility of an investigational drug as part of treatment.
The data presented at ASCO were based on results observed in patients at high risk of relapse using up-front tumor profiling. Patients were treated with weekly standard chemotherapy (paclitaxel) for 12 weeks, with or without pembrolizumab, followed by doxorubicin and cyclophosphamide every three weeks for four cycles. Sixty-nine patients were adaptively randomized to receive pembrolizumab in the trial from December 2015 until November 2016. In total, 46 patients have undergone surgery; the other 23 have on-therapy MRI assessments.
“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 Forero, also a senior scientist at the 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.”
Precision medicine techniques and drug combinations are the latest tools in harnessing the power of getting different therapies to work in more people. UAB’s breast cancer team is aggressively conducting tumor profiling early in treatment, and combining conventional treatments such as chemotherapy and radiation with new drug therapies.
“The bottom line is that the results of this trial can help make investigational drugs available to more women in the future,” Forero said. “We are hopeful that there will be new and better options available to our patients right at diagnosis.”