Dr. Costa on the Implications of the KEYNOTE-522 Trial in TNBC

Ricardo Costa, MD, MSC, a medical oncologist in the Department of Breast Oncology at Moffitt Cancer Center, discusses the implications of the phase 3 KEYNOTE-522 trial (NCT03036488) trial in patients with high-risk, early-stage triple-negative breast cancer (TNBC). 

In July 2021, the FDA approved pembrolizumab (Keytruda) for the treatment of this patient population when combined with chemotherapy in the neoadjuvant setting, followed by single-agent adjuvant treatment after surgery, based on data from KEYNOTE-522.

The phase 3 trial randomly assigned 1174 patients in a 2:1 fashion to receive neoadjuvant chemotherapy with or without pembrolizumab. The trial enrolled patients with both node-negative and -positive disease, and tumor stage ranged from T1c N1/N2 to T2 to T4 and N0 to N2, per AJCC criteria.

The practice-changing results of KEYNOTE-522 made neoadjuvant pembrolizumab plus chemotherapy and adjuvant pembrolizumab monotherapy one of the standard options for patients with high-risk, early-stage TNBC, Costa starts. This includes patients with a T2 tumor or an N1-positive breast cancer at presentation, which are subsets of disease associated with a higher chance of cancer recurrence compared with other histologies such as estrogen receptor–positive breast cancer, Costa explains.

The trial met its 2 primary end points for pathologic complete response (pCR) and event-free survival (EFS). Patients treated in the pembrolizumab arm achieved a pCR rate of 64.8%, compared with 51.2% for patients in the placebo arm. Those in the pembrolizumab arm also achieved an estimated 3-year EFS rate of 84.5%, compared with 76.8% for those in the placebo arm.

These data suggested that pembrolizumab adds to the probability of shrinking the tumor and eliminating its invasive component, and the addition of pembrolizumab was associated with a higher chance of EFS, Costa continues. Based on a stratified analysis of PD-L1 expression, PD-L1 is prognostic, but not predictive, of benefit, Costa adds. This means that it is not necessary to check for PD-L1 expression prior to recommending pembrolizumab combined with chemotherapy in this high-risk patient population, Costa concludes.