{"entity":{"id":"paper-keynote-522-n-engl-j-med-2020","kind":"paper","name":"Pembrolizumab for Early Triple-Negative Breast Cancer","aka":[],"tldr":"Published report from the KEYNOTE-522 trial registered as NCT03036488, in New England Journal of Medicine (2020), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Previous trials showed promising antitumor activity and an acceptable safety profile associated with pembrolizumab in patients with early triple-negative breast cancer. Whether the addition of pembrolizumab to neoadjuvant chemotherapy would significantly increase the percentage of patients with early triple-negative breast cancer who have a pathological complete response (defined as no invasive cancer in the breast and negative nodes) at definitive surgery is unclear.\n\nMethods: In this phase 3 trial, we randomly assigned (in a 2:1 ratio) patients with previously untreated stage II or stage III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) every 3 weeks plus paclitaxel and carboplatin (784 patients; the pembrolizumab-chemotherapy group) or placebo every 3 weeks plus paclitaxel and carboplatin (390 patients; the placebo-chemotherapy group); the two groups then received an additional four cycles of pembrolizumab or placebo, and both groups received doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After definitive surgery, the patients received adjuvant pembrolizumab or placebo every 3 weeks for up to nine cycles. The primary end points were a pathological complete response at the time of definitive surgery and event-free survival in the intention-to-treat population.\n\nResults: At the first interim analysis, among the first 602 patients who underwent randomization, the percentage of patients with a pathological complete response was 64.8% (95% confidence interval [CI], 59.9 to 69.5) in the pembrolizumab-chemotherapy group and 51.2% (95% CI, 44.1 to 58.3) in the placebo-chemotherapy group (estimated treatment difference, 13.6 percentage points; 95% CI, 5.4 to 21.8; P<0.001). After a median follow-up of 15.5 months (range, 2.7 to 25.0), 58 of 784 patients (7.4%) in the pembrolizumab-chemotherapy group and 46 of 390 patients (11.8%) in the placebo-chemotherapy group had disease progression that precluded definitive surgery, had local or distant recurrence or a second primary tumor, or died from any cause (hazard ratio, 0.63; 95% CI, 0.43 to 0.93). Across all treatment phases, the incidence of treatment-related adverse events of grade 3 or higher was 78.0% in the pembrolizumab-chemotherapy group and 73.0% in the placebo-chemotherapy group, including death in 0.4% (3 patients) and 0.3% (1 patient), respectively.\n\nConclusions: Among patients with early triple-negative breast cancer, the percentage with a pathological complete response was significantly higher among those who received pembrolizumab plus neoadjuvant chemotherapy than among those who received placebo plus neoadjuvant chemotherapy. (Funded by Merck Sharp & Dohme [a subsidiary of Merck]; KEYNOTE-522 ClinicalTrials.gov number, NCT03036488.).\n\nIndexed on Europe PMC as PubMed record 32101663 (DOI 10.1056/nejmoa1910549). Its abstract cites the registry id NCT03036488, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2020","url":"https://doi.org/10.1056/nejmoa1910549"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32101663/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32101663"},{"label":"ClinicalTrials.gov NCT03036488","url":"https://clinicaltrials.gov/study/NCT03036488"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-522"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/nejmoa1910549","pmid":"32101663","authors":"Schmid P, Cortes J, Pusztai L, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03036488 with the most citations, so it is the natural first reading for anyone following the KEYNOTE-522 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},"route":"/key-papers/paper-keynote-522-n-engl-j-med-2020/","neighbours":{"trial":[{"id":"keynote-522","kind":"trial","name":"KEYNOTE-522","route":"/trials/keynote-522/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"idea":[{"id":"idea-post-neoadjuvant-adc","kind":"idea","name":"ADC for residual disease after KEYNOTE-522","route":"/ideas/idea-post-neoadjuvant-adc/"},{"id":"idea-neoadjuvant-adc-io","kind":"idea","name":"Neoadjuvant ADC + IO replacing anthracycline chemotherapy in TNBC","route":"/ideas/idea-neoadjuvant-adc-io/"}]}}