ONCOLOGY
OBSTETRICS & GYNECOLOGY
CONFERENCE UPDATE

Long-term survival benefit of pembrolizumab in high-risk early TNBC: Final analysis of the phase 3 KEYNOTE-522 study

18 Sep 2026

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STUDY DESIGN

Interim analyses of the phase 3 KEYNOTE-522 study demonstrated that neoadjuvant pembrolizumab + chemotherapy followed by adjuvant pembrolizumab significantly improved pathological complete response (pCR), event-free survival (EFS), and overall survival (OS) vs. neoadjuvant chemotherapy alone in patients with high-risk, early-stage triple-negative breast cancer (TNBC).1 Based on these findings, the regimen has been approved for patients with high-risk, early-stage TNBC and has been incorporated into standard treatment guidelines.1

Results from the final analysis of KEYNOTE-522 were reported after a median follow-up of approximately 94 months.1 Eligible patients were ≥18 years of age with newly diagnosed high-risk early-stage TNBC (T1c N1-2 or T2-4 N0-2), Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and available tumor tissue for PD-L1 assessment.1 Patients were randomized 2:1 to receive neoadjuvant pembrolizumab 200mg every 3 weeks (Q3W) (n=784) or placebo (n=390), both in combination with four cycles of paclitaxel + carboplatin followed by four cycles of doxorubicin or epirubicin + cyclophosphamide.1 Following definitive surgery, patients received adjuvant pembrolizumab or placebo for up to nine cycles or until disease recurrence or unacceptable toxicity.1

Randomization was stratified by nodal status (positive vs. negative), tumor size (T1/T2 vs. T3/T4), and carboplatin schedule (weekly vs. every 3 weeks).1 Baseline characteristics were generally well balanced between the treatment groups.1 The primary endpoints were pCR (ypT0/Tis ypN0) and EFS, defined as the time from randomization to disease progression that precluded definitive surgery, local or distant recurrence, second primary cancer, or death from any cause, while OS was the key secondary endpoint.1

FINDINGS

Primary endpoints:
  • The primary endpoints were pCR and EFS1
  • After a median follow-up of 93.8 months, pembrolizumab + chemotherapy followed by adjuvant pembrolizumab improved EFS vs. chemotherapy alone (HR=0.68; 95% CI: 0.54-0.86)1
  • EFS benefit was generally consistent across prespecified subgroups, including PD-L1 status, nodal status, tumor size, and carboplatin schedule1
  • EFS benefit was observed regardless of pCR status, with comparable HRs among patients who achieved pCR (HR=0.68; 95% CI: 0.44-1.07) and those who did not (HR=0.78; 95% CI: 0.59-1.03), despite a larger absolute EFS benefit in patients without pCR1
Secondary endpoint:
  • The key secondary endpoint assessed was OS1
  • At a median follow-up of 93.8 months, pembrolizumab reduced the risk of death by 36% vs. placebo (HR=0.64; 95% CI: 0.49-0.85)1
  • OS benefit was similarly observed across prespecified subgroups, including age, PD-L1 status, carboplatin schedule, nodal status, and tumor size1
  • The OS benefit was observed irrespective of pCR status, with comparable HRs among patients who achieved pCR (HR=0.64; 95% CI: 0.37-1.14) and those who did not (HR=0.76; 95% CI: 0.55-1.03)1
  • The addition of pembrolizumab reduced the risk of distant progression or distant recurrence by 36% vs. placebo (HR=0.64; 95% CI: 0.49-0.83)1
Safety:
  • The safety profile remained manageable and was consistent with previous analyses and the known safety profiles of pembrolizumab and chemotherapy, with no new safety signals identified during long-term follow-up1
  • The incidence of treatment-related adverse events (TRAEs) was comparable between treatment groups, with most adverse events considered chemotherapy-related1
  • TRAEs of any grade occurred in 98.9% of patients receiving pembrolizumab vs. 99.7% receiving placebo, with grade 3-5 TRAEs occurred in 77.1% and 73.3% of patients, respectively1
  • Immune-mediated adverse events occurred more frequently with pembrolizumab vs. placebo (35.0% vs. 13.1%), including grade 3-5 events reported in 13.0% and 1.5% of patients, respectively1
  • Hypothyroidism and hyperthyroidism were among the most common immune-mediated adverse events1

 

The sustained improvements in pCR, EFS, and OS support neoadjuvant pembrolizumab + platinum-containing chemotherapy followed by adjuvant pembrolizumab as a standard-of-care treatment option for patients with high-risk, early-stage TNBC

Dr. Javier Cortes
International Breast Cancer Center,
Barcelona, Spain

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References

  1. Schmid P, 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. Presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2026; May 29-June 2, 2026.

PEMBROLIZUMAB
TRIPLE-NEGATIVE BREAST CANCER
NEOADJUVANT THERAPY

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