Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for high-risk early-stage TNBC: Final analysis results from the phase 3 KEYNOTE-522 study.

507 Background: KEYNOTE-522 (NCT03036488) showed statistically significant and clinically meaningful improvements in pCR, EFS, and OS with the addition of pembrolizumab (pembro) to chemotherapy (chemo) in participants (pts) with high-risk early-stage TNBC. Here, we present updated results from the final analysis. Methods: Eligible pts with previously untreated, non-metastatic, centrally confirmed TNBC (stage T1c N1-2 or T2-4 N0-2 per AJCC) were randomized 2:1 to neoadjuvant pembro 200 mg Q3W or placebo (pbo), both given with 4 cycles of paclitaxel + carboplatin, then 4 cycles of doxorubicin or epirubicin + cyclophosphamide. After definitive surgery, pts received adjuvant pembro or pbo for 9 cycles or until recurrence or unacceptable toxicity. Dual primary endpoints are pCR (ypT0/Tis ypN0) and EFS (time from randomization to disease progression that precluded definitive surgery, local/distant recurrence, second primary cancer, or death from any cause); OS is the key secondary endpoint. Results: 1174 pts were randomized to pembro (n = 784) or pbo (n = 390). At the data cutoff date (October 14, 2025), median follow-up (range) was 93.8 mo (84.7-102.8). The 7-yr EFS rate (95% CI) was 78.3% (75.3-81.1) in the pembro group vs 69.8% (65.0-74.2) in the pbo group; the HR was 0.68 (95% CI, 0.54-0.86). The 7-yr OS rate (95% CI) was 85.1% (82.5-87.5) in the pembro group vs 77.2% (72.7-81.1) in the pbo group; the HR was 0.64 (95% CI, 0.49-0.85). The benefit of pembro on EFS and OS was generally consistent across most prespecified subgroups, including those defined by PD-L1 expression, nodal status, and disease stage. Rates of grade ≥3 treatment-related AEs were 77.1% in the pembro group and 73.3% in the pbo group (death incidence, 0.5% vs 0.3%, respectively); rates of any grade immune-mediated AEs were 35.0% vs 13.1%, respectively. Conclusions: After a median follow-up of 7.8 years, neoadjuvant pembro + chemo followed by adjuvant pembro continues to show a clinically meaningful survival benefit compared with neoadjuvant chemo alone in pts with high-risk early-stage TNBC. Clinical trial information: NCT03036488 .