Pembrolizumab Plus Neoadjuvant Therapy Improved Response Rates in TNBC

June 20, 2017

Results from a nationwide clinical trial, which were presented at the 2017 ASCO Annual Meeting, indicate that adding pembrolizumab to standard therapy before surgery offers the potential for improving outcomes in this patient population.

It may be possible to improve outcomes in patients with locally advanced triple-negative (TNBC) or hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancers by combining tumor profiling with conventional treatments.

Results from a nationwide clinical trial, which were presented (abstract 506) at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6 in Chicago, indicate that adding pembrolizumab to standard therapy before surgery offers the potential for improving outcomes in this patient population.

The I-SPY 2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis 2) is testing whether adding investigational drugs to standard chemotherapy, based on molecular tests, is better than standard chemotherapy alone prior to surgery. The trial is a novel collaborative effort among academic investigators from 20 major cancer research centers across the United States, Quantum Leap Healthcare Collaborative, the US Food and Drug Administration (FDA), and the Foundation for the National Institutes of Health Cancer Biomarkers Consortium, pharmaceutical and biotech companies, and patient advocates.

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.

So far, the findings look promising in an initial series of patients. “We found that pembrolizumab essentially more than tripled the rate of pathologic complete responses in HER2-negative patients in the I-SPY 2 TRIAL,” said Andres Forero, MD, who is a professor in the Division of Hematology and Oncology, and head of the breast cancer program at the University of Alabama at Birmingham.

The data presented at ASCO were based on results observed in patients at high-risk of relapse based on tumor profiling. Patients were treated with weekly standard chemotherapy (paclitaxel) for 12 weeks, with or without pembrolizumab, followed by doxorubicin and cyclophosphamide every 3 weeks for 4 cycles.

For this investigation, 69 patients were adaptively randomized to receive pembrolizumab in the trial from December 2015 until November 2016. In total, 46 patients have undergone surgery and the remaining other 23 have on-therapy MRI assessments.

In 29 TNBC patients, pembrolizumab increased raw pathological complete response by > 50% and estimated pathological complete response rates by 40%; in 40 HR-positive/HER-negative patients, it did so by 13% and 21%, respectively.

In terms of treatment-related adverse events (AEs), five patients had immune-related grade 3 AEs (one with hypophysitis and four with adrenal insufficiency).

Forero said not all breast cancers are the same and there continues to be a significant gap in the treatment options available for patients with certain breast cancer subtypes, particularly TNBC. These new findings set the stage for a shift in treatment toward combination therapies that can begin at the time of diagnosis.