# KEYNOTE-522

Source: https://onco.cc/trials/keynote-522/  
OnCo record `keynote-522` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The trial that added immunotherapy to pre-surgery chemotherapy for triple-negative breast cancer and, uniquely, improved survival.

## Summary

1,174 patients. pCR 64.8% vs 51.2%; event-free survival at 5 years 81.2% vs 72.2%; 7-year EFS 78.3% vs 69.8% and OS 85.1% vs 77.2% (ASCO 2026 update). Defines the standard of care for stage II-III TNBC. Open questions: whether adjuvant pembrolizumab is needed after pCR (OptimICE-pCR) and how to escalate for residual disease.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-04
- Registry id: NCT03036488
- Phase: 3
- Setting: Early-stage (II-III) TNBC: pembrolizumab + chemotherapy before surgery, pembrolizumab after
- Sponsor: Merck
- Enrolled: 1174
- Result: EFS HR 0.63; OS HR 0.66 (5-year); 7-year OS 85.1% vs 77.2%.
- Outcomes: Pathologic complete response (ypT0/Tis ypN0): Pembrolizumab + chemotherapy 64.8% vs Placebo + chemotherapy 51.2%; Event-free survival at 5 years: Pembrolizumab + chemotherapy 81.2% vs Placebo + chemotherapy 72.2%, HR 0.65; Overall survival at 5 years: Pembrolizumab + chemotherapy 86.6% vs Placebo + chemotherapy 81.7%, HR 0.66; Event-free survival at 7 years: Pembrolizumab + chemotherapy 78.3% vs Placebo + chemotherapy 69.8%; Overall survival at 7 years: Pembrolizumab + chemotherapy 85.1% vs Placebo + chemotherapy 77.2%
- Replication: Single pivotal trial, but the EFS and OS benefits held through the 5- and 7-year analyses; consistent with IMpassion031 (atezolizumab, pCR only) and with real-world neoadjuvant pembrolizumab series.

## Notes

- Design (NEJM 2020): 1,174 patients with untreated stage II or III triple-negative breast cancer randomised 2 to 1 to pembrolizumab 200 mg or placebo every 3 weeks with four cycles of paclitaxel and carboplatin then four of doxorubicin or epirubicin with cyclophosphamide, surgery, then nine cycles of adjuvant pembrolizumab or placebo. Pathological complete response 64.8 versus 51.2 percent (first 602 patients); event-free survival at 36 months 84.5 versus 76.8 percent (hazard ratio 0.63, NEJM 2022); overall survival at 60 months 86.6 versus 81.7 percent (p 0.002, median follow-up 75.1 months, NEJM 2024). Residual cancer burden analysis (Annals of Oncology 2024): pembrolizumab reduced events in RCB-0, 1 and 2 (hazard ratios 0.70, 0.92, 0.52) but not RCB-3 (1.24).
- UK sites (registry, 7): Colchester General Hospital, Barts Cancer Institute, St George's Hospital London, Maidstone Hospital, James Cook University Hospital Middlesbrough, Nottingham University Hospitals, Royal Cornwall Hospitals Truro. NICE TA851 (14 December 2022) commissions the regimen in England.
- Label safety (Keytruda, 778 treated patients): serious adverse reactions 44 percent, fatal 0.9 percent, discontinuation of pembrolizumab 20 percent, most often for raised transaminases and rash.

## Sources

- ClinicalTrials.gov NCT03036488: https://clinicaltrials.gov/study/NCT03036488
- KEYNOTE-522 pathological complete response (NEJM 2020): https://doi.org/10.1056/NEJMoa1910549
- KEYNOTE-522 event-free survival (NEJM 2022): https://doi.org/10.1056/NEJMoa2112651
- KEYNOTE-522 overall survival (NEJM 2024): https://doi.org/10.1056/NEJMoa2409932
- KEYNOTE-522 event-free survival by residual cancer burden (Annals of Oncology 2024): https://doi.org/10.1016/j.annonc.2024.02.002
- NICE TA851 (14 December 2022): https://www.nice.org.uk/guidance/ta851

## Connected records

- cancers: [Basal-like 1 triple-negative breast cancer (BL1)](https://onco.cc/cancers/tnbc-basal-like-1/), [Basal-like 2 triple-negative breast cancer (BL2)](https://onco.cc/cancers/tnbc-basal-like-2/), [Carcinoma with medullary pattern (medullary breast cancer)](https://onco.cc/cancers/medullary-pattern-breast-carcinoma/), [Early triple-negative breast cancer](https://onco.cc/cancers/tnbc-early/), [Inflammatory breast cancer](https://onco.cc/cancers/inflammatory-breast-cancer/), [Luminal androgen receptor triple-negative breast cancer (LAR)](https://onco.cc/cancers/tnbc-luminal-androgen-receptor/), [Mesenchymal stem-like triple-negative breast cancer (MSL)](https://onco.cc/cancers/tnbc-mesenchymal-stem-like/), [Mesenchymal triple-negative breast cancer (M)](https://onco.cc/cancers/tnbc-mesenchymal/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- companies: [Merck & Co. (MSD)](https://onco.cc/companies/merck/)
- terms: [Confirmatory trial](https://onco.cc/terms/confirmatory-trial/), [Data maturity (immature vs mature survival data)](https://onco.cc/terms/data-maturity/), [De-escalation, escalation and response-adapted therapy](https://onco.cc/terms/de-escalation/), [Event-free / disease-free survival (EFS, DFS, iDFS, RFS)](https://onco.cc/terms/efs/), [Invasive disease-free survival (iDFS)](https://onco.cc/terms/idfs/), [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/), [Palliation in advanced triple-negative breast cancer: brain, bone, pleura, skin and end of life](https://onco.cc/terms/tnbc-symptom-control-palliation/), [Pathologic complete response (pCR)](https://onco.cc/terms/pcr/), [PD-L1 combined positive score 10 in triple-negative breast cancer](https://onco.cc/terms/pd-l1-cps-10-tnbc/), [Phase 1, 2 and 3 trials](https://onco.cc/terms/trial-phases/), [Pivotal (registrational) trial](https://onco.cc/terms/pivotal-trial/), [Residual cancer burden (RCB)](https://onco.cc/terms/rcb/), [Residual disease after neoadjuvant therapy in triple-negative breast cancer: the decision point](https://onco.cc/terms/tnbc-residual-disease-decision/), [Surrogate endpoint](https://onco.cc/terms/surrogate-endpoint/), [Surrogate endpoint validation: which stand-ins have earned trust](https://onco.cc/terms/surrogate-validation/), [Trial lifecycle: from protocol to label](https://onco.cc/terms/trial-lifecycle/), [Trial protocol and statistical analysis plan](https://onco.cc/terms/trial-protocol/), [Trial registration and results reporting (ClinicalTrials.gov, EU CTR)](https://onco.cc/terms/trial-registration/)
- trials: [A-BRAVE](https://onco.cc/trials/a-brave/), [ALEXANDRA / IMpassion030](https://onco.cc/trials/impassion030/), [ASCENT-05 / OptimICE-RD (AFT-65, GBG 119, NSABP B-63)](https://onco.cc/trials/ascent-05/), [BrighTNess](https://onco.cc/trials/brightness/), [c-TRAK TN](https://onco.cc/trials/c-trak-tn/), [CALGB 40603 (Alliance)](https://onco.cc/trials/calgb-40603/), [ECOG-ACRIN EA1131](https://onco.cc/trials/ea1131/), [GeparDouze / NSABP B-59](https://onco.cc/trials/gepardouze/), [GeparSixto](https://onco.cc/trials/geparsixto/), [NeoPACT](https://onco.cc/trials/neopact/), [NeoTRIP (NeoTRIPaPDL1)](https://onco.cc/trials/neotrip/), [OptimICE-pCR (A012103)](https://onco.cc/trials/optimice-pcr/), [PARTNER](https://onco.cc/trials/partner/), [PHOENIX DDR/Anti-PD-L1](https://onco.cc/trials/phoenix/), [SCARLET (SWOG S2212)](https://onco.cc/trials/scarlet-s2212/), [SWOG S1418 / NRG BR006](https://onco.cc/trials/swog-s1418/), [TROPION-Breast03](https://onco.cc/trials/tropion-breast03/)
- people: [Peter Schmid](https://onco.cc/people/peter-schmid/), [Rebecca Dent](https://onco.cc/people/rebecca-dent/), [Sherene Loi](https://onco.cc/people/loi-sherene/)
- key papers: [Breast Cancer, Version 4.2026, NCCN Clinical Practice Guidelines In Oncology](https://onco.cc/key-papers/paper-nccn-breast-cancer-v4-2026-jnccn-2026/), [Early breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up](https://onco.cc/key-papers/paper-esmo-early-breast-cancer-guideline-ann-oncol-2024/), [Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance)](https://onco.cc/key-papers/paper-sikov-calgb-40603-carboplatin-bevacizumab-jco-2015/), [KEYNOTE-522: adding pembrolizumab before and after surgery in early triple-negative breast cancer](https://onco.cc/key-papers/paper-keynote-522-nejm-2022/), [Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer](https://onco.cc/key-papers/paper-keynote-522-n-engl-j-med-2024-update/), [Pembrolizumab for Early Triple-Negative Breast Cancer](https://onco.cc/key-papers/paper-keynote-522-n-engl-j-med-2020/), [Sustained benefit of adjuvant olaparib in women with germline BRCA1- and BRCA2-associated high-risk HER2-negative early breast cancer: updated results from the OlympiA phase III trial](https://onco.cc/key-papers/paper-olympia-6-year-update-ann-oncol-2026/), [Tailoring treatment to cancer risk and patient preference: the 2025 St Gallen International Breast Cancer Consensus Statement on individualizing therapy for patients with early breast cancer](https://onco.cc/key-papers/paper-st-gallen-2025-consensus-ann-oncol-2025/), [Use of Immune Checkpoint Inhibitor Pembrolizumab in the Treatment of High-Risk, Early-Stage Triple-Negative Breast Cancer: ASCO Guideline Rapid Recommendation Update](https://onco.cc/key-papers/paper-asco-pembrolizumab-early-tnbc-rapid-update-jco-2022/)
- roadmaps: [Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity](https://onco.cc/roadmaps/immunotherapy-roadmap/), [Surgery roadmap: radical operations → less surgery → no surgery when a drug has done the work](https://onco.cc/roadmaps/surgery-roadmap/), [TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line](https://onco.cc/roadmaps/tnbc-history/), [Trial modernisation roadmap: the randomised trial → platforms and adaptive designs → decentralised, pragmatic and always-on](https://onco.cc/roadmaps/trial-modernisation-roadmap/), [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/)
- ideas: [ADC for residual disease after KEYNOTE-522](https://onco.cc/ideas/idea-post-neoadjuvant-adc/), [ctDNA-guided adjuvant decisions after residual disease: escalate the positive, spare the negative](https://onco.cc/ideas/idea-tnbc-ctdna-guided-adjuvant-decisions/), [Give exceptional responders less: pembrolizumab omission after complete response, anthracycline-free regimens and chemotherapy omission in lymphocyte-rich stage I disease](https://onco.cc/ideas/idea-tnbc-de-escalation-for-exceptional-responders/), [Neoadjuvant ADC + IO replacing anthracycline chemotherapy in TNBC](https://onco.cc/ideas/idea-neoadjuvant-adc-io/), [Pre-surgery platform trials that test combinations on pathological response in months](https://onco.cc/ideas/idea-tr2-neoadjuvant-combo-platform/)
- institutions: [Dana-Farber Brigham Cancer Center](https://onco.cc/institutions/dana-farber/)

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