Triple-negative breast cancer is an aggressive type of cancer that usually has a high rate of disease recurrence (returning) within the first 5 years after diagnosis. Many breast cancers involve a hormone known as estrogen receptor (ER) or progesterone receptor (PR) or the HER2 protein, but in about 15% to 20% of patients, the cancer doesn’t involve any of these 3 biomarkers, which explains the name “triple-negative breast cancer.”
Therefore, this type of breast cancer does not respond to therapies that target any of these 3 biomarkers (ER, PR, or HER2), which makes this a difficult cancer to treat. Until recently, no targeted therapies or immunotherapies were available for patients with this cancer.
In March 2019, the FDA approved the first immunotherapy, Tecentriq (atezolizumab), in combination with chemotherapy, for patients with metastatic (spreading) triple-negative breast cancer.
More recently, in July 2019, the drug maker Merck announced new results from a phase 3 clinical trial known as KEYNOTE-522, showing that its immunotherapy Keytruda (pembrolizumab), an anti–PD-1 antibody, or PD-1 inhibitor, in combination with chemotherapy, achieved pathologic complete response as neoadjuvant (before surgery) therapy in patients with triple-negative breast cancer. A pathologic complete response is defined as a lack of any signs of cancer in tissue samples after neoadjuvant therapy and surgery.
Keytruda is the first PD-1 inhibitor and first immunotherapy to demonstrate, in combination with chemotherapy, an increase in the number of patients whose cancer showed complete response to neo-adjuvant therapy in patients with triple-negative breast cancer, regardless of the patient’s PD-1 or PD-L1 status. So far in this clinical trial, the side effects seen with Keytruda were consistent with the drug’s safety profile in previously reported studies, and no new safety concerns were identified.
“These findings from this innovatively designed trial with Keytruda mark the first time an anti-PD-1 therapy plus chemotherapy has demonstrated a statistically significant improvement in pathological complete response rate as a neoadjuvant, or pre-surgical, segment of treatment for triple-negative breast cancer,” said Roger M. Perlmutter, MD, PhD, President, Merck Research Laboratories.
The KEYNOTE-522 trial is comparing the benefits of Keytruda plus chemotherapy versus placebo plus chemotherapy for patients with triple-negative breast cancer. The study enrolled 1,174 patients with triple-negative breast cancer who were divided into 2 groups. One group received Keytruda plus chemotherapy as neoadjuvant (before surgery) therapy, followed by Keytruda alone as adjuvant (after surgery) therapy. The second group received placebo plus chemotherapy (with paclitaxel and carboplatin), followed by placebo plus cyclophosphamide and either doxorubicin or epirubicin, followed by placebo alone as adjuvant therapy.
These positive results may lead to the FDA approval of Keytruda as the second immunotherapy for patients with triple-negative breast cancer.