Breast Cancer · Medical Oncology · Neoadjuvant / Adjuvant Immunotherapy

KEYNOTE-522

In previously untreated stage II–III triple-negative breast cancer, does adding pembrolizumab to neoadjuvant chemotherapy and continuing it after surgery improve pathological complete response, event-free survival and overall survival compared with chemotherapy alone?

Population

1,174 patients with previously untreated stage II or III TNBC

Randomisation

Pembrolizumab–chemotherapy 784; placebo–chemotherapy 390

Experimental treatment

Pembrolizumab 200 mg every 3 weeks with paclitaxel–carboplatin, then anthracycline–cyclophosphamide; after surgery, pembrolizumab for up to 9 cycles

Control

Matching placebo with the same chemotherapy and post-operative placebo schedule

Absolute Effect

Pathological complete response

64.8% vs 51.2%

Absolute increase: 13.6 percentage points. Descriptive NNT for one additional pCR ≈ 8.

Overall survival at 60 months

86.6% vs 81.7%

Absolute survival difference: 4.9 percentage points. Reciprocal absolute difference ≈ 20 patients per additional survivor at 5 years; this is a time-specific estimate, not a trial-reported NNT.

Source-reported outcomes

pCR at surgery · pembrolizumab + chemotherapy vs placebo + chemotherapy

pembro arm

64.8%

control arm

51.2%

Overall survival at 5 years · final OS analysis, median follow-up 75.1 months

pembro arm

86.6%

control arm

81.7%

Bars use the published percentages on a 0–100% scale. The pCR and 5-year OS results come from separate analyses/publications.

Event-free survival

At 36 months, estimated EFS was 84.5% with pembrolizumab vs 76.8% with placebo, an absolute difference of 7.7 percentage points (HR for event or death 0.63; 95% CI 0.48–0.82; P<.001). The regimen improved EFS as well as pCR.

Safety and treatment burden

Adverse events were consistent with the known profiles of chemotherapy and pembrolizumab. Immune-mediated toxicities can be serious or persistent and require active monitoring and management. The trial evaluates the complete perioperative pembrolizumab strategy; it does not isolate the independent contribution of the adjuvant phase. No single NNH is assigned here because a comparable fixed-time harm endpoint has not been selected for this summary.

Clinical interpretation

KEYNOTE-522 supports perioperative pembrolizumab with platinum-, taxane- and anthracycline-containing chemotherapy for eligible patients with high-risk stage II–III TNBC. This is a distinct evidence base from NSABP B-59/GeparDouze, which tested atezolizumab and did not meet its primary EFS endpoint. Do not treat the two checkpoint inhibitors or trial results as interchangeable.

Current-practice context · reviewed 18 October 2026

For eligible patients with high-risk early TNBC, the pembrolizumab-plus-chemotherapy regimen followed by adjuvant pembrolizumab is an established perioperative option. The pivotal trial enrolled patients with stage II–III disease regardless of PD-L1 expression. Confirm local regulatory access, contraindications, stage/eligibility criteria and current guideline recommendations before treatment.

Primary and authoritative sources

Schmid P, et al. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020;382:810–821. Primary pCR report ↗

Schmid P, et al. Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer. N Engl J Med. 2022;386:556–567. Primary EFS report ↗

Schmid P, et al. Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer. N Engl J Med. 2024;391:1981–1991. Final OS report ↗

ClinicalTrials.gov. KEYNOTE-522, NCT03036488. Trial registry ↗

ASCO guideline rapid recommendation update. Guideline publication ↗