At the 2023 San Antonio Breast Cancer Symposium, 5-year data from the phase 3 KEYNOTE-522 trial highlighted the sustained survival benefits of neoadjuvant pembrolizumab (Keytruda) plus chemotherapy followed by adjuvant pembrolizumab in patients with high-risk, early-stage triple-negative breast cancer (TNBC). The study, with a median follow-up of 63.1 months, reported a 5-year event-free survival (EFS) rate of 81.3% for the pembrolizumab group compared to 72.3% for the placebo group (HR, 0.63; 95% CI, 0.49-0.81).
Peter Schmid, FRCP, MD, PhD, emphasized the significance of these findings, stating that they reinforce the regimen's role as a standard-of-care for this patient population. The trial enrolled patients aged 18 or older with newly diagnosed TNBC, requiring an ECOG performance status of 0 or 1 and a tissue sample for PD-L1 assessment.
Participants were randomized to receive either pembrolizumab or placebo alongside chemotherapy before surgery, followed by adjuvant pembrolizumab or placebo. The study's primary endpoints were pathologic complete response (pCR) and EFS, with secondary endpoints including safety and pCR rates in specific subgroups.
Interim analyses revealed a significant increase in pCR rates with pembrolizumab and a notable improvement in EFS, leading to FDA approval of the regimen in July 2021. Subgroup analyses further confirmed the EFS benefit across various patient demographics and disease stages, with particular efficacy noted in patients achieving pCR.
Despite the promising results, the study's overall survival follow-up continues, with biomarker findings expected in 2024. The incidence of brain metastases as a first EFS event was low in both groups, with a slightly lower rate in the pembrolizumab group.
This research underscores the potential of pembrolizumab in enhancing outcomes for patients with early-stage TNBC, marking a significant advancement in the treatment landscape for this aggressive cancer subtype.
