Pembrolizumab Holds Promise in Breast Cancer, Early Studies Suggest

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Rita Nanda, MD

Pembrolizumab Findings Spark Interest

There is excitement about immunotherapy in breast cancer, and this study shows that, as in other tumor types, a small proportion of patients may respond, and those who do respond tend to be long-term responders.

—Rita Nanda, MD

Single-agent treatment with the immunotherapy drug pembrolizumab produced a “signal of activity” and led to some durable responses 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.1

“There is excitement about immunotherapy for the treatment of triple-negative breast cancer. What this study shows, as is the case for other tumor types, is that a proportion of patients appear to respond to therapy. And those who do respond tend to be long-term responders,” Dr. Nanda indicated at a press briefing.

Pembrolizumab is a humanized monoclonal antibody that targets the programmed cell death protein 1 (PD-1). 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 already 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, most of whom had received at least three prior chemotherapies for advanced disease. Patients were only eligible if their tumors were positive for PD-L1 expression. Patients received pembrolizumab at 10 mg/kg every 2 weeks until progression of disease 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, and 15 (55.6%) had progressive disease. 

“The current standard of care for this heavily pretreated triple-negative breast cancer population is chemotherapy, and in comparison to chemotherapy, an 18% response rate is of interest,” Dr. Nanda suggested. “Furthermore, those patients who did experience a response had responses that lasted 40 weeks or more, which is very exciting when you think about how well tolerated this drug appears to be.”

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.

“Pembrolizumab showed an acceptable safety and tolerability profile in patients with 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.” ■

Disclosure: Dr. Nanda reported no potential conflicts of interest.


1. Nanda R, et al: San Antonio Breast Cancer Symposium. Abstract S1-09. Presented December 10, 2014.


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