I say onward to the rational combinations, so we can drive these response rates up…. Let’s move on these findings so that we can benefit our other breast cancer patients.
—Mary L. Disis, MD
Study discussant 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 cancer, and renal cancer. She pointed out that when anti–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 that 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.”
Good Target for Immunotherapy
The ASCO Post also spoke with Lajos Pusztai, MD, DPhil, Professor of Medicine, Chief of Breast Medical Oncology and Co-Director of Cancer Genetics Research Program at Yale Cancer Center, New Haven, Connecticut. He agreed that the overall response rate of 18% to the single agent is almost as high as that seen in other malignancies where anti–PD-1 agents are being studied.
“Remember, the single-agent activity of trastuzumab [Herceptin] in HER2-positive patients was 20%,” he added. “We will learn how to leverage the single-agent activity of these drugs.” This will most likely be achieved by giving these drugs in combination with other immunotherapies, as is being studied in melanoma right now, he predicted.
To Dr. Pusztai, the findings are particularly “exciting” because triple-negative breast cancer has been completely lacking in new, effective treatments. Meeting this unmet need is partly driving the interest in anti–PD-1 agents in triple-negative cancer, but so is the biology of this subtype: triple-negative tumors are a good target for immunotherapy, he pointed out.
“Based on indirect data, the most dramatic prognostic effect of an immune presence is in triple-negative breast cancer. This is the breast cancer with the highest degree of immune infiltration,” he noted. “This is very exciting. For a long time we have known that patients with a lot of tumor-infiltrating lymphocytes do better, but we haven’t known if this was cause or association. Now we have drugs with which to test this prospectively.”
Dr. Pusztai is involved in the development of an adjuvant study of pembrolizumab in triple-negative breast cancer. He indicated that several companies are in a race to develop these drugs, “which will probably change practice…. We are in a new era of cancer therapies.” ■
Disclosure: Dr. Disis received grant funding from Seattle Genetics, VentiRx, and EMD Serono and has stock in VentiRx and Epithany. Dr. Pusztai reported no potential conflicts of interest.
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