Hope Rugo, MD
Pembrolizumab (Keytruda) may have similar potential in ER-positive/HER2-negative advanced breast cancer as was previously shown in triple-negative breast cancer (TNBC), says Hope S. Rugo, MD, professor of Medicine and director of Breast Oncology and Clinical Trials Education at the University of California San Francisco Helen Diller Family Comprehensive Cancer Center.
Rugo was the lead investigator on the phase Ib KEYNOTE-028 trial, a basket trial that demonstrated an overall response rate (ORR) of 12% (n = 3; 95% CI, 2.5-31.2) in PD-L1–positive patients with ER-positive/HER2-negative breast cancer.1
Previously reported data from the phase Ib KEYNOTE-012 trial showed that pembrolizumab had an ORR of 18.5% in patients with PD-L1–positive TNBC.2
“I think we are seeing the same durability we saw in triple-negative breast cancer,” says Rugo, who presented the phase Ib KEYNOTE-028 trial at the San Antonio Breast Cancer Symposium in December 2015. “There was a lower percent of PD-L1 positivity and a lower response rate, but the results were still very reasonable in patients with ER-positive disease treated with a single immunotherapy.”
To better understand the phase Ib KEYNOTE-028 trial and the impact of its results thus far, OncLive
spoke with Rugo about the design, findings, and next steps for the trial.
OncLive: How was the KEYNOTE-028 trial designed?
: The KEYNOTE-028 trial is a basket or multi-cohort phase Ib trial. It is certainly not by any means the first-in-human study. However, the reason why these types of trials are often called phase I trials is because many different cancers are included. Only phase I units have the capability of taking care of patients with so many different kinds of cancer.
This trial included 20 cancers. Six patients have reported response rates from 11.5% up to 30%. The ER-positive/HER2-negative breast cancer cohort is the seventh cohort to report. At the 2014 San Antonio Breast Cancer Symposium, data were presented on ER-negative/HER2-negative breast cancer—known as triple-negative disease—that showed that pembrolizumab resulted in a response rate of 18%. In some of these patients, the response rate was very durable.
How was this cohort selected?
We did this cohort of ER-positive/HER2-negative breast cancer, which we know has a PD-L1 expression rate of somewhere between 4% and 20%. Previous studies have suggested that expression is more common in women who have more proliferative luminal B type disease. We tested women with PD-L1–expressing metastatic ER-positive breast cancer who had received chemotherapy in some setting.