Long-Term Results Reinforce a Practice-Changing Regimen

Final results from the phase 3 KEYNOTE-522 study confirm that adding pembrolizumab to neoadjuvant chemotherapy, followed by adjuvant pembrolizumab after surgery, provides sustained benefit for patients with previously untreated, high-risk, early-stage triple-negative breast cancer (TNBC). With approximately 8 years of median follow-up, the regimen continued to improve event-free survival (EFS) and overall survival (OS) compared with neoadjuvant chemotherapy followed by adjuvant placebo.

Study Design and Treatment

KEYNOTE-522 enrolled 1174 patients with newly diagnosed, nonmetastatic TNBC and randomized them 2:1 to pembrolizumab or placebo. In the neoadjuvant phase, patients received 4 cycles of paclitaxel plus carboplatin followed by 4 cycles of doxorubicin or epirubicin plus cyclophosphamide. Pembrolizumab 200 mg or placebo was given every 3 weeks with chemotherapy. After definitive surgery, patients continued their assigned pembrolizumab or placebo for 9 cycles or until recurrence or unacceptable toxicity.

The coprimary end points were pathologic complete response (pCR) and EFS, with OS as the key secondary end point. The final analysis included 784 patients assigned to pembrolizumab and 390 assigned to placebo. Baseline characteristics were balanced between groups, including tumor size, nodal status, carboplatin schedule, and PD-L1 expression.

Event-Free and Overall Survival Benefits Persist

At the final analysis, the 7-year EFS rate was 78.3% with the pembrolizumab regimen and 69.8% with placebo, corresponding to a hazard ratio of 0.68. The 7-year OS rate was 85.1% versus 77.2%, respectively, with a hazard ratio of 0.66. The long-term survival curves remained separated, supporting the durability of benefit observed in earlier analyses.

Benefits for both EFS and OS were generally consistent across prespecified subgroups, including those defined by nodal status, tumor size, carboplatin schedule, age, and PD-L1 expression. The presentation also showed favorable long-term outcomes regardless of whether patients achieved a pCR. However, because analyses by pathologic response were based on a posttreatment outcome, they should be interpreted cautiously.

Distant Disease Control and the Importance of pCR

At 7 years, distant progression-free or distant recurrence-free survival was 82.9% with pembrolizumab plus chemotherapy followed by pembrolizumab and 74.2% with chemotherapy followed by placebo. pCR remained an important prognostic marker. Patients who achieved a pCR had the most favorable EFS and OS in both treatment groups, while the pembrolizumab regimen also improved outcomes among patients without a pCR.

Safety Remains Consistent With Prior Analyses

The final safety findings were consistent with the established profiles of pembrolizumab and chemotherapy, and no new safety signals emerged. Grade 3 to 5 treatment-related adverse events occurred in 77.1% of patients in the pembrolizumab group and 73.3% in the placebo group. Treatment-related discontinuation of any study drug occurred in 27.6% and 14.1%, respectively.

Immune-mediated adverse events occurred more frequently with pembrolizumab. Events of any grade were reported in 35.0% of the pembrolizumab group and 13.1% of the placebo group; grade 3 to 5 events occurred in 13.0% and 1.5%, respectively. These findings underscore the need for proactive recognition and management of immune-related toxicities throughout neoadjuvant and adjuvant treatment.

Clinical Takeaway

After approximately 8 years of follow-up, KEYNOTE-522 demonstrates durable improvements in EFS, OS, and distant disease control. The final analysis strengthens the evidence that neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab can reduce recurrence risk and improve long-term survival for patients with high-risk early-stage TNBC.

References

1. Schmid P, Cortes J, Dent R, et al. Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for high-risk early-stage triple-negative breast cancer (TNBC): final analysis results from the phase 3 KEYNOTE-522 study. Slide presentation. Presented at: 2026 American Society of Clinical Oncology Annual Meeting; Abstract 507.
2. Schmid P, Cortes J, Dent RA, et al. 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. J Clin Oncol. 2026;44(suppl). Abstract 507. doi:10.1200/JCO.2026.44.16_suppl.507