Pembrolizumab in Triple-Negative Breast Cancer: Emerging New Treatment Modality


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We are in a new era of cancer therapies.
— Lajos Pusztai, MD, DPhil

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, commented on ­KEYNOTE-012. He remarked that the overall response rate of 18.5% to the single agent is similar to response rates seen in other malignancies where anti–PD-1 (programmed cell death protein 1) agents are being studied or approved and is also similar or even higher than what single-agent chemotherapy would induce in this patient population.

“Remember, the single-agent activity of trastuzumab [Herceptin] in HER2-positive patients was also around 20%,” he added. “We will learn how to leverage the single-agent activity of these drugs.” This may be achieved by giving these drugs in combination with other immunotherapies, as is being studied in melanoma right now, or with chemotherapies, he predicted.

To Dr. Pusztai, the findings from KEYNOTE-012 are particularly “exciting” because triple-negative breast cancer has been lacking in new, effective treatments other than chemotherapies and prolonged duration of response to chemotherapy, as was seen with pembrolizumab ­(Keytruda), are very rare. 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 often contain many tumor-infiltrating lymphocytes, he pointed out.

“Tumor infiltrating lymphocytes predict for better prognosis and also greater chemotherapy sensitivity in stage I-III, triple-negative breast cancer and in highly proliferative estrogen receptor–positive cancers,” he noted. For a long time, we have known that patients with a lot of tumor-infiltrating lymphocytes do better, but we were not sure if the immune cells have caused the better outcome or were a mere coincidence. Now we have drugs to test this prospectively.”

Dr. Pusztai leads a neoadjuvant immunotherapy trial for triple-negative breast cancer and is also involved in the development of an adjuvant trial of pembrolizumab for patients who have residual cancer after neoadjuvant chemotherapy. He added “We are in a new era of cancer therapies that we hope will extend to breast cancer.” ■

Disclosure: Dr. Pusztai has received clinical trial research support and honorarium from Merck.

Reference

1. Nanda R, Chow LQ, Dees EC, et al: Pembrolizumab in patients with advanced triple-negative breast cancer: Phase Ib KEYNOTE-012 study. J Clin Oncol. May 2, 2016 (early release online).


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