Clinical Trial of Pembrolizumab Shows Improved Event-Free Survival in High-Risk, Early-Stage Triple-Negative Breast Cancer

The KEYNOTE-522 trial met its dual primary endpoints of pathologic complete response and event-free survival, showing a statistically significant and clinically meaningful improvement in EFS compared to neoadjuvant chemotherapy alone.

A pivotal study of pembrolizumab (Keytruda, Merck) in combination with chemotherapy has shown statistically significant improvements in event-free survival (EFS) among patients with high-risk, early-stage triple-negative breast cancer (TNBC), according to a press release.

The KEYNOTE-522 trial enrolled 1174 patients who were randomized to 1 of 2 regimens. The investigative arm received pembrolizumab plus paclitaxel and carboplatin for 4 cycles. This was followed by pembrolizumab plus cyclophosphamide and either doxorubicin or epirubicin for 4 cycles as neoadjuvant therapy, before receiving 9 cycles of pembrolizumab as adjuvant therapy post-surgery. The control group received a placebo in place of pembrolizumab during these cycles.

TNBC is an aggressive form of breast cancer that has a high recurrence rate within the first 5 years following diagnosis, according to the press release. Although some breast cancers may test positive for estrogen receptors, progesterone receptors, or overexpression of human epidermal growth factor receptor 2, TNBC tests negative for all 3. Approximately 15% to 20% of all breast cancers are TNBC, and it tends to be more common in women under the age of 40, who are African American, or who have a BRCA1 mutation.

Pembrolizumab works by increasing the ability of the body’s immune system to help detect and fight tumor cells, according to the press release. The KEYNOTE-522 trial met its dual primary endpoint of EFS and showed a statistically significant and clinically meaningful improvement compared to neoadjuvant chemotherapy alone.

“Keytruda is the first immunotherapy to show positive results for event-free survival in patients with high-risk early-stage TNBC, a particularly aggressive form of breast cancer,” said Roy Baynes, MMed, PhD, FCP, senior vice president, head of global clinical development, and chief medical officer of Merck Research Laboratories, in a press release. “The improvement in pathological complete response rates initially observed following pre-operative treatment was encouraging, and now that we are seeing the data mature after 4 years to include a statistically significant improvement in event-free survival, we look forward to working with the FDA and other global authorities to bring this new option to patients as quickly as possible.”

An earlier analysis of the pathologic complete response from KEYNOTE-522 also showed a statistically significant increase in patients with early-stage TNBC, regardless of PD-L1 status. This was the trial’s other dual primary endpoint, as announced in 2019. Furthermore, the investigators found a safety profile consistent with that observed in other studies and identified no new safety signals.


Merck Announces Phase 3 KEYNOTE-522 Trial Met Dual Primary Endpoint of Event-Free Survival (EFS) in Patients With High-Risk Early-Stage Triple-Negative Breast Cancer (TNBC) [news release]. Merck; May 13, 2021. Accessed May 13, 2021.