FDA Approval Summary: Pembrolizumab for Neoadjuvant and Adjuvant Treatment of Patients with High-Risk Early-Stage Triple Negative Breast Cancer.

On July 26, 2021, the Food and Drug Administration granted approval to pembrolizumab in combination with chemotherapy for neoadjuvant treatment and then continued as a single agent for adjuvant treatment following surgery for patients with high-risk, early-stage triple negative breast cancer (TNBC). Approval was based on results from KEYNOTE-522, an ongoing randomized (2:1) trial evaluating pembrolizumab or placebo in combination with chemotherapy for neoadjuvant treatment and then as a single agent for adjuvant treatment. The co-primary endpoints were pathological complete response (pCR) rate and event free survival (EFS). The trial demonstrated an improvement in pCR and EFS in the pembrolizumab arm compared to the control arm. The number of patients who experienced an EFS event was 123 (16%) and 93 (24%), respectively (HR: 0.63, 95% CI: 0.48-0.82, p=0.00031). Patients on the pembrolizumab arm experienced EFS benefit regardless of tumor PD-L1 status. The absolute pCR rate improvement with the addition of pembrolizumab was 7.5% (95% CI: 1.6%, 13.4%). Among patients receiving pembrolizumab, 44% experienced an immune-related adverse reaction. This article summarizes FDA's review of pembrolizumab and the data supporting the favorable benefit-risk assessment.