SABCS 2014: Pembrolizumab Holds Promise in Breast Cancer, Early Studies Suggest


Key Points

  • The anti–PD-1 agent pembrolizumab produced an 18.5% response rate in patients with metastatic triple-negative breast cancer.
  •  For responders, median duration of response has not been reached; 6-month progression-free survival was 23.3%.

Single-agent treatment with the immunotherapy drug pembrolizumab (Keytruda) produced a “signal of activity” and led to some durable response, in patients with metastatic triple-negative breast cancer, Rita Nanda, MD, of the University of Chicago, reported at the 2014 San Antonio Breast Cancer Symposium (Abstract S1-09).

“There is excitement about immunotherapy in breast cancer, and what this study shows, as in other tumor types, is that a small proportion of patients may respond and that those who do respond tend to be long-term responders. There is durability of response that we don’t see with other therapies,” Dr. Nanda indicated at a press briefing.

Pembrolizumab is a humanized monoclonal antibody that blocks the interaction of the programmed cell death protein-1 (PD-1) receptor and its ligands, PD-L1 and PD-L2. This releases the PD-1 pathway-mediated inhibition of the immune response, in effect “taking the brakes off” the immune system to allow it to attack the tumor. Pembrolizumab is approved for the treatment of advanced melanoma.

KEYNOTE-012 Details

The phase IB KEYNOTE-012 trial recruited 32 patients with metastatic triple-negative breast cancer that had either relapsed after treatment of early-stage disease or progressed on therapy for advanced disease; most patients had received at least three prior therapies. All patients stained positive for PD-L1 expression. Patients received 10 mg/kg pembrolizumab every 2 weeks until progression or unacceptable toxicity.

Among 27 patients with measurable disease (by RECIST 1.1 criteria), the overall response rate was 18.5%, including one (3.7%) complete response and four (14.8%) partial responses. In addition, seven patients (25.9%) had stable disease, 12 (44.4%) had progressive disease, and three (11.1%) were not assessed.

“There is not a standard of care for this population of patients, and when you think of how heavily pretreated they were, in comparison to chemotherapy an 18% response rate is of interest,” she suggested.

At a median follow-up of 9.9 months, the median duration of response has not been reached, ranging from 15 to 40 months. Median progression-free survival was 1.9 months, and the progression-free survival rate at 6 months was 23.3%, Dr. Nanda reported.

Toxicity Profile

Adverse events of any grade were observed in 56% of patients; grade 3 events were observed in 12.5% and grade 4 in 3.1%. Three patients (9.4%) had a serious adverse event, one of which resulted in death due to disseminated intravascular coagulation.

“Pembrolizumab showed an acceptable safety and tolerability profile in patients with fairly heavily pretreated, PD-L1–positive, advanced triple-negative breast cancer,” Dr. Nanda concluded. “Responses were durable, and three of five responders have been on treatment for at least 11 months.”

A phase II study of pembrolizumab in advanced triple-negative disease is planned for the first half of 2015.

‘Let’s Move on These Findings’

Mary L. Disis, MD, Professor of Medicine and Associate Dean of Translational Science at the University of Washington, Seattle, commented that the response rate, approaching 20%, is “in the ballpark” of those observed in melanoma, lung, and renal cancer. She pointed out that when PD-1 agents are combined with other active agents—especially MEK inhibitors, as is done in melanoma—response rates can exceed 50%.

“We are seeing the biology, response rates, and toxicity we see in other diseases,” she pointed out.

“I say onward to the rational combinations, so we can drive these response rates up,” Dr. Disis said. “Let’s not wait. Let’s move on these findings so that we can benefit our other breast cancer patients.”

The study was funded by Merck. Dr. Nanda reported no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.