• Peter Schmid, Javier Cortes, Lajos Pusztai, Heather McArthur, Sherko Kümmel, Jonas Bergh, Carsten Denkert, Yeon Hee Park, Rina Hui, Nadia Harbeck, Masato Takahashi, Theodoros Foukakis, Peter A Fasching, Fatima Cardoso, Michael Untch, Liyi Jia, Vassiliki Karantza, Jing Zhao, Gursel Aktan, Rebecca Dent, Joyce O'Shaughnessy, and KEYNOTE-522 Investigators.
• From Barts Cancer Institute, Queen Mary University of London, London (P.S.); International Oncology Bureau Institute of Oncology, Quirón Group, Madrid, and Vall d'Hebron Institute of Oncology, Barcelona (J.C.) - both in Spain; Yale School of Medicine, Yale Cancer Center, New Haven, CT (L.P.); Cedars-Sinai Medical Center, Los Angeles (H.M.); Kliniken Essen-Mitte, Essen (S.K.), the Institute of Pathology, Philipps-University Marburg and University of Marburg, Marburg (C.D.), the Breast Center, Department of Obstetrics and Gynecology and Comprehensive Cancer Center Ludwig Maximilian University of Munich, University of Munich, Munich (N.H.), University Hospital Erlangen, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-European Metropolitan Region of Nuremberg, Erlangen (P.A.F.), and the Breast Cancer Center, Helios Klinikum Berlin-Buch, Berlin (M.U.) - all in Germany; the Department of Oncology-Pathology, Karolinska Institutet and Breast Cancer Center, Theme Cancer, Karolinska University Hospital, Solna, Sweden (J.B., T.F.); Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (Y.H.P.); Westmead Breast Cancer Institute, Westmead Hospital and the University of Sydney, Sydney (R.H.); Department of Breast Surgery, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan (M.T.); the Breast Unit, Champalimaud Clinical Center, Champalimaud Foundation, Lisbon, Portugal (F.C.); Merck, Kenilworth, NJ (L.J., V.K., J.Z., G.A.); the National Cancer Center Singapore, Duke-National University of Singapore Medical School, Singapore (R.D.); and Baylor University Medical Center, Texas Oncology and US Oncology, Dallas (J.O.).
• N. Engl. J. Med. 2020 Feb 27; 382 (9): 810-821.

BackgroundPrevious 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.MethodsIn 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.ResultsAt 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.ConclusionsAmong 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.).Copyright © 2020 Massachusetts Medical Society.

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