• Peter Schmid, Javier Cortes, Rebecca Dent, Lajos Pusztai, Heather McArthur, Sherko Kümmel, Jonas Bergh, Carsten Denkert, Yeon Hee Park, Rina Hui, Nadia Harbeck, Masato Takahashi, Michael Untch, Peter A Fasching, Fatima Cardoso, Jay Andersen, Debra Patt, Michael Danso, Marta Ferreira, Marie-Ange Mouret-Reynier, Seock-Ah Im, Jin-Hee Ahn, Maria Gion, Sally Baron-Hay, Jean-François Boileau, Yu Ding, Konstantinos Tryfonidis, Gursel Aktan, Vassiliki Karantza, Joyce O'Shaughnessy, and KEYNOTE-522 Investigators.
• From Barts Cancer Institute, Queen Mary University of London, London (P.S.); International Breast Cancer Center, Quironsalud Group, and Vall d'Hebron Institute of Oncology, Barcelona (J.C.), and the Faculty of Biomedical and Health Sciences, Department of Medicine, Universidad Europea de Madrid (J.C.), and Ramon y Cajal University Hospital (M.G.), Madrid; the National Cancer Center Singapore, Duke-National University of Singapore Medical School, Singapore (R.D.); Yale School of Medicine, Yale Cancer Center, New Haven, CT (L.P.); the University of Texas Southwestern Medical Center (H.M.), and Baylor University Medical Center, Texas Oncology, U.S. Oncology Network (J.O.), Dallas, and Texas Oncology, U.S. Oncology Network, Austin (D.P.); the Breast Unit, Kliniken Essen-Mitte, Essen, Charité-Universitätsmedizin Berlin, the Department of Gynecology with Breast Center (S.K.) and the Breast Cancer Center, Helios Klinikum Berlin-Buch (M.U.), Berlin, the Institute of Pathology, Philipps-University Marburg and University Hospital Marburg, Marburg (C.D.), the Breast Center, Department of Obstetrics and Gynecology and Comprehensive Cancer Center Munich, LMU University Hospital, Munich (N.H.), and the Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-European Metropolitan Region of Nuremberg, University Hospital Erlangen, Erlangen (P.A.F.) - all in Germany; the Department of Oncology-Pathology, Karolinska Institutet, and Breast Cancer Center, Cancer Theme, Karolinska University Hospital, Karolinska Comprehensive Cancer Center, Solna, Sweden (J.B.); Samsung Medical Center, Sungkyunkwan University School of Medicine (Y.H.P.), Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine (S.-A.I.), and Asan Medical Center, University of Ulsan College of Medicine (J.-H.A.) - all in Seoul, South Korea; Westmead Breast Cancer Institute, Westmead Hospital and the University of Sydney (R.H.), and Royal North Shore Hospital (S.B.-H.) - both in Sydney; Hokkaido Cancer Center, Sapporo, Japan (M.T.); the Breast Unit, Champalimaud Clinical Center-Champalimaud Foundation, Lisbon (F.C.), and Instituto Português de Oncologia do Porto Francisco Gentil, Porto (M.F.) - both in Portugal; Compass Oncology, U.S. Oncology Network, Portland, OR (J.A.); Virginia Oncology Associates, U.S. Oncology Network, Norfolk (M.D.); Centre Jean-Perrin, Clermont-Ferrand, France (M.-A.M.-R.); McGill University, Segal Cancer Centre, Jewish General Hospital, Montreal (J.-F.B.); and Merck, Kenilworth, NJ (Y.D., K.T., G.A., V.K.).
• N. Engl. J. Med. 2022 Feb 10; 386 (6): 556-567.

BackgroundThe addition of pembrolizumab to neoadjuvant chemotherapy led to a significantly higher percentage of patients with early triple-negative breast cancer having a pathological complete response (defined as no invasive cancer in the breast and negative nodes) at definitive surgery in an earlier analysis of this phase 3 trial of neoadjuvant and adjuvant therapy. The primary results regarding event-free survival in this trial have not been reported.MethodsWe randomly assigned, in a 2:1 ratio, patients with previously untreated stage II or III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After definitive surgery, patients received adjuvant pembrolizumab (pembrolizumab-chemotherapy group) or placebo (placebo-chemotherapy group) every 3 weeks for up to nine cycles. The primary end points were pathological complete response (the results for which have been reported previously) and event-free survival, defined as the time from randomization to the date of disease progression that precluded definitive surgery, local or distant recurrence, occurrence of a second primary cancer, or death from any cause. Safety was also assessed.ResultsOf the 1174 patients who underwent randomization, 784 were assigned to the pembrolizumab-chemotherapy group and 390 to the placebo-chemotherapy group. The median follow-up at this fourth planned interim analysis (data cutoff, March 23, 2021) was 39.1 months. The estimated event-free survival at 36 months was 84.5% (95% confidence interval [CI], 81.7 to 86.9) in the pembrolizumab-chemotherapy group, as compared with 76.8% (95% CI, 72.2 to 80.7) in the placebo-chemotherapy group (hazard ratio for event or death, 0.63; 95% CI, 0.48 to 0.82; P<0.001). Adverse events occurred predominantly during the neoadjuvant phase and were consistent with the established safety profiles of pembrolizumab and chemotherapy.ConclusionsIn patients with early triple-negative breast cancer, neoadjuvant pembrolizumab plus chemotherapy, followed by adjuvant pembrolizumab after surgery, resulted in significantly longer event-free survival than neoadjuvant chemotherapy alone. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; KEYNOTE-522 ClinicalTrials.gov number, NCT03036488.).Copyright © 2022 Massachusetts Medical Society.

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