# KEYNOTE-522: adding pembrolizumab before and after surgery in early triple-negative breast cancer

Source: https://onco.cc/key-papers/paper-keynote-522-nejm-2022/  
OnCo record `paper-keynote-522-nejm-2022` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Adding the immunotherapy pembrolizumab to chemotherapy before surgery, then continuing it afterwards, cut the risk of relapse or death by about a third in stage II-III triple-negative breast cancer and later improved survival.

## Summary

Phase 3, double-blind trial randomising 1,174 patients with untreated stage II-III triple-negative breast cancer (2:1) to neoadjuvant pembrolizumab or placebo plus carboplatin-paclitaxel then anthracycline-cyclophosphamide, followed by surgery and nine cycles of adjuvant pembrolizumab or placebo. Dual primary endpoints were pathological complete response (pCR) and event-free survival (EFS).

The 2020 report showed pCR 64.8% vs 51.2%. This 2022 report showed the EFS benefit: 36-month EFS 84.5% vs 76.8% (HR 0.63). A 2024 report added an overall survival benefit (5-year OS 86.6% vs 81.7%, HR 0.66). It established chemo-immunotherapy as the standard for stage II-III TNBC regardless of PD-L1 status.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2022
- DOI: 10.1056/NEJMoa2112651
- Authors: Schmid P, Cortes J, Dent R, et al.
- Findings: pCR (ypT0/Tis ypN0) 64.8% with pembrolizumab vs 51.2% with placebo, a 13.6-point absolute gain (2020 interim report).; 36-month event-free survival 84.5% vs 76.8%; HR for event or death 0.63 (95% CI 0.48-0.82).; Benefit was seen regardless of PD-L1 expression (CPS), unlike in the metastatic setting.; Patients with residual disease still did worse than those with pCR, but pembrolizumab improved EFS in both groups.; 5-year overall survival 86.6% vs 81.7%, HR 0.66 (2024 update).
- What it means: For stage II-III triple-negative breast cancer, chemotherapy plus pembrolizumab before surgery and pembrolizumab alone afterwards is now the standard approach worldwide, and the survival gain is real, not just a surrogate. It does not apply to stage I disease or to hormone-receptor-positive or HER2-positive cancers. The price is a year of immunotherapy with a meaningful chance of a permanent endocrine side effect such as hypothyroidism or adrenal insufficiency.
- Caveats: The trial cannot say whether the adjuvant phase of pembrolizumab is needed for patients who reach pCR; de-escalation trials are testing this.; Immune-related adverse events (thyroid, adrenal, pituitary) are often permanent.; Carboplatin was part of the backbone in both arms, so the trial does not isolate the contribution of platinum.; The control arm did not include capecitabine for residual disease, which some regard as a weaker comparator.

## Sources

- NEJM 2022 (EFS): https://doi.org/10.1056/NEJMoa2112651
- NEJM 2020 (pCR): https://doi.org/10.1056/NEJMoa1910549
- ClinicalTrials.gov NCT03036488: https://clinicaltrials.gov/study/NCT03036488

## Connected records

- ideas: [ADC for residual disease after KEYNOTE-522](https://onco.cc/ideas/idea-post-neoadjuvant-adc/), [ctDNA-triggered escalation in early TNBC](https://onco.cc/ideas/idea-ctdna-escalation-tnbc/)
- cancers: [Inflammatory breast cancer](https://onco.cc/cancers/inflammatory-breast-cancer/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Platinum agents](https://onco.cc/technologies/platinum/)
- targets: [PD-1](https://onco.cc/targets/pd1/)
- 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: [Combined positive score (CPS)](https://onco.cc/terms/cps/), [Event-free / disease-free survival (EFS, DFS, iDFS, RFS)](https://onco.cc/terms/efs/), [Immune-related adverse events (irAEs)](https://onco.cc/terms/irae/), [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/), [Pathologic complete response (pCR)](https://onco.cc/terms/pcr/), [Residual cancer burden (RCB)](https://onco.cc/terms/rcb/)
- trials: [KEYNOTE-522](https://onco.cc/trials/keynote-522/)
- people: [Carsten Denkert](https://onco.cc/people/carsten-denkert/), [Javier Cortés](https://onco.cc/people/javier-cortes/), [Jonas Bergh](https://onco.cc/people/jonas-bergh/), [Peter Schmid](https://onco.cc/people/peter-schmid/), [Yeon Hee Park](https://onco.cc/people/park-yeon-hee/)
- bottlenecks: [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/), [No one can predict who responds to immunotherapy](https://onco.cc/bottlenecks/b-immunotherapy-response/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- roadmaps: [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/)

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