Elizabeth A. Mittendorf, MD, PhD
There is still a lot to be learned regarding the use of checkpoint inhibitors in breast cancer, but the field is advancing rapidly. Several agents have shown potential in recent trials.
In the phase Ib JAVELIN study, treatment with the PD-L1 inhibitor avelumab demonstrated promising results for patients with metastatic breast cancer. After a median follow-up of 10 months, the overall response rate (ORR) in all patients with PD-L1-expressing metastatic breast cancer was 33.3%. The highest response rate of 44.4% was seen in patients with PD-L1- positive triple-negative breast cancer (TNBC), although other subtypes also saw benefit.
The trial includes patients with tumors that are HER2- negative/HR-positive (42.9%), triple-negative (34.5%), and HER2-positive (15.5%). Around 7% of breast cancer cases in the trial were not identified as a particular subtype. In the full population of the study, the ORR included 1 complete response and 7 partial responses. An additional 23.2% of patients experienced stable disease with avelumab, for a disease control rate of 28%. Of those who responded, 5 had TNBC (8.6%) and 4 were PD-L1-positive. Responses were also observed in patients with HER2-negative/HR-positive breast cancer (2.8%) and in those with HER2-positive disease (3.8%).1 In addition, in the ongoing phase Ib KEYNOTE-028 basket trial—which is evaluating pembrolizumab (Keytruda) in patients with PD-L1-positive advanced solid tumors of all types—an ORR of 12% was seen in patients with ER+/HER2- advanced breast cancer.
In previously reported data from the phase Ib KEYNOTE-012 trial, pembrolizumab demonstrated an ORR of 18.5% in patients with PD-L1–positive TNBC. Elizabeth Mittendorf, MD, PhD is an associate professor in the Department of Surgical Oncology at the University of Texas MD Anderson Cancer Center.
In the following interview with OncLive
, Mittendorf talked about checkpoint inhibition studies in TNBC, potential ways to make other subtypes more immunogenic to improve response, the role of PD-1, and what’s next in the field of immunotherapy in breast cancer.
OncLive: How has the use of checkpoint inhibition in breast cancer evolved in the past year?
: We have additional data now for multiple agents in TNBC; this time last year we just had pembrolizumab.
There is a cooperative group study trial proposed to evaluate the role of checkpoint blockade in TNBC patients who receive neoadjuvant chemotherapy and have persistent disease. Our group at MD Anderson is just starting a trial looking at checkpoint blockade in combination with chemotherapy in the neoadjuvant setting for what we are defining as high-risk TNBC.
Very importantly, at SABCS (San Antonio Breast Cancer Symposium) in December 2015 there were data presented on the use of checkpoint inhibitors in subtypes of breast cancer other than TNBC. The JAVELIN trial included ER-positive, HER2-positive, and TNBC breast cancers. There are also several ongoing studies and concepts in development that are moving checkpoint inhibitors, which are showing themselves to be safe, into the neoadjuvant setting as well as the adjuvant setting.