{"entity":{"id":"paper-keynote-522-nejm-2022","kind":"paper","name":"KEYNOTE-522: adding pembrolizumab before and after surgery in early triple-negative breast cancer","aka":[],"tldr":"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).\n\nThe 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.","asOf":"2026-09-08","links":[{"label":"NEJM 2022 (EFS)","url":"https://doi.org/10.1056/NEJMoa2112651"},{"label":"NEJM 2020 (pCR)","url":"https://doi.org/10.1056/NEJMoa1910549"},{"label":"ClinicalTrials.gov NCT03036488","url":"https://clinicaltrials.gov/study/NCT03036488"}],"tags":[],"related":["idea-post-neoadjuvant-adc","idea-ctdna-escalation-tnbc"],"cancers":["tnbc"],"sections":[],"technologies":["checkpoint-inhibitor","cytotoxic-chemotherapy","platinum"],"targets":["pd1"],"drugs":["pembrolizumab","carboplatin","paclitaxel"],"companies":["merck"],"institutions":[],"pathways":[],"terms":["pcr","efs","neoadjuvant-adjuvant","cps","irae","rcb"],"trials":["keynote-522"],"people":["javier-cortes","jonas-bergh","park-yeon-hee","carsten-denkert"],"bottlenecks":["b-immunotherapy-response","b-toxicity-qol","b-dormancy-mrd"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2112651","authors":"Schmid P, Cortes J, Dent R, et al.","paperType":"rct","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)."],"whatItMeans":"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."],"changedPractice":true,"participants":1174},"route":"/key-papers/paper-keynote-522-nejm-2022/","neighbours":{"idea":[{"id":"idea-post-neoadjuvant-adc","kind":"idea","name":"ADC for residual disease after KEYNOTE-522","route":"/ideas/idea-post-neoadjuvant-adc/"},{"id":"idea-ctdna-escalation-tnbc","kind":"idea","name":"ctDNA-triggered escalation in early TNBC","route":"/ideas/idea-ctdna-escalation-tnbc/"}],"cancer":[{"id":"inflammatory-breast-cancer","kind":"cancer","name":"Inflammatory breast cancer","route":"/cancers/inflammatory-breast-cancer/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"platinum","kind":"technology","name":"Platinum agents","route":"/technologies/platinum/"}],"target":[{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"company":[{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"}],"term":[{"id":"cps","kind":"term","name":"Combined positive score (CPS)","route":"/terms/cps/"},{"id":"efs","kind":"term","name":"Event-free / disease-free survival (EFS, DFS, iDFS, RFS)","route":"/terms/efs/"},{"id":"irae","kind":"term","name":"Immune-related adverse events (irAEs)","route":"/terms/irae/"},{"id":"neoadjuvant-adjuvant","kind":"term","name":"Neoadjuvant / adjuvant / perioperative","route":"/terms/neoadjuvant-adjuvant/"},{"id":"pcr","kind":"term","name":"Pathologic complete response (pCR)","route":"/terms/pcr/"},{"id":"rcb","kind":"term","name":"Residual cancer burden (RCB)","route":"/terms/rcb/"}],"trial":[{"id":"keynote-522","kind":"trial","name":"KEYNOTE-522","route":"/trials/keynote-522/"}],"person":[{"id":"carsten-denkert","kind":"person","name":"Carsten Denkert","route":"/people/carsten-denkert/"},{"id":"javier-cortes","kind":"person","name":"Javier Cortés","route":"/people/javier-cortes/"},{"id":"jonas-bergh","kind":"person","name":"Jonas Bergh","route":"/people/jonas-bergh/"},{"id":"peter-schmid","kind":"person","name":"Peter Schmid","route":"/people/peter-schmid/"},{"id":"park-yeon-hee","kind":"person","name":"Yeon Hee Park","route":"/people/park-yeon-hee/"}],"bottleneck":[{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"roadmap":[{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","route":"/roadmaps/tnbc-roadmap/"}]}}