Nearly 65% of patients whose disease had spread to lymph nodes showed no signs of cancer following a regimen of Keytruda plus chemotherapy compared with those who received chemotherapy alone.
Adding Keytruda (pembrolizumab) to chemotherapy before surgery and radiation, followed by another dose of Keytruda after, showed greater responses in patients with early-stage triple-negative breast cancer compared with patients who received chemotherapy alone, according to results from the KEYNOTE-522 clinical trial.
The latest data from the phase 3 study were presented during the 2019 San Antonio Breast Cancer Symposium (SABCS) and included a subgroup analyses of patients with lymph node involvement.
Triple-negative breast cancer is an aggressive type of the disease and has a higher rate of recurrence within the first five years, according to study author Dr. Peter Schmid, professor of cancer medicine at Barts Cancer Institute in London. That risk of recurrence is even higher if the disease spreads to lymph nodes.
The current standard of care for early stage triple-negative breast cancer is chemotherapy alone. “Currently, the pCR (pathologic complete response) rate for standard chemotherapy treatment using an anthracycline and taxane combination is about 40%, or about 50% if a platinum-based drug is added to the combination,” Schmid said in a press release. “There continues to be a significant need for new regimens that can increase the pCR rate and increase long-term, event-free survival for patients with triple-negative breast cancer.”
Pathologic complete response means there are no signs of cancer in tissue samples removed during surgery or biopsy after chemotherapy and radiation treatment, according to the National Cancer Institute.
The study enrolled 1,174 patients over the age of 18 who had previously untreated, non-metastatic, centrally confirmed triple-negative breast cancer. They were chosen at random to receive Keytruda plus chemotherapy or placebo plus chemotherapy as initial treatment before surgery and radiation therapy. After these treatments, patients were given Keytruda or placebo until Patients received either adjuvant pembrolizumab or placebo until recurrence or when they could no longer tolerate the medication.
Findings presented Dec. 12 during SABCS showed that 64.8% of patients in the Keytruda plus chemotherapy group had a pathologic complete response compared with 44.1% of patients in the chemotherapy alone group. High rates of pathologic complete response were also seen in patients with stage 3 disease, the researchers noted.
When asked during a press briefing how Keytruda could have similar effects in patients regardless of whether they were PD-L1 positive or negative, Schmid hypothesized that it was because all patients in the trial had early-stage breast cancer.
“In advanced disease, we see a clear difference between patients who have PD-L1 positive and PD-L1 negative tumors in terms of benefit from immune therapy,” Schmid said during a press briefing. “My personal theory is that this is because tumor plasticity is very high in early disease.”
Treatments targeting the PD-1/PD-L1 pathway were previously shown to be effective for patients with metastatic triple-negative breast cancer. Keytruda, which is a type of immunotherapy, works to block the protein PD-1 and may help the immune system kill cancer cells.
Despite promising results, the study was limited by the fact that it is still ongoing. “After 15 months of follow-up, we see a strong favorable trend for event-free survival, but it has not yet met the predefined boundaries for statistical significance,” Schmid said. “(However), our results suggest that adding pembrolizumab to neoadjuvant (treatment given before surgery) chemotherapy is beneficial for patients with the most aggressive disease and the highest unmet need. I think the results have the potential to be practice-changing.”