• Charles E Geyer, Michael Untch, Chiun-Sheng Huang, Max S Mano, Eleftherios P Mamounas, Norman Wolmark, Priya Rastogi, Andreas Schneeweiss, Andres Redondo, Hans H Fischer, Véronique D'Hondt, Alison K Conlin, Valentina Guarneri, Irene L Wapnir, Christian Jackisch, Claudia Arce-Salinas, Peter A Fasching, Michael P DiGiovanna, John P Crown, Pia Wuelfing, Zhimin Shao, Elena Rota Caremoli, Hervé R Bonnefoi, Bryan T Hennessy, Ljiljana Stamatovic, Hugo Castro-Salguero, Adam M Brufsky, Adam Knott, Asna Siddiqui, Chiara Lambertini, Thomas Boulet, Beatrice Nyawira, Eleonora Restuccia, Sibylle Loibl, and KATHERINE Study Group.
• From the National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation (C.E.G., E.P.M., N.W., P.R., I.L.W., A.M.B.) and University of Pittsburgh School of Medicine-UPMC Hillman Cancer Center (C.E.G., N.W., P.R., A.M.B.) - both in Pittsburgh; AGO-B and Helios Klinikum Berlin-Buch, Berlin (M.U.), the National Center for Tumor Diseases, Heidelberg University Hospital, and German Cancer Research Center, Heidelberg (A.S.), Evangelische Kliniken Gelsenkirchen, Gelsenkirchen (H.H.F.), Arbeitsgemeinschaft Gynäkologische Onkologie-Breast and Sana Klinikum Offenbach, Offenbach (C.J.), the Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen (P.A.F.), German Breast Group, Neu-Isenburg (P.W., S.L.), and the Center for Hematology and Oncology Bethanien, Goethe University, Frankfurt (S.L.) - all in Germany; National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (C.-S.H.); Instituto do Câncer do Estado de São Paulo, São Paulo (M.S.M.); Orlando Health Cancer Institute, Orlando, FL (E.P.M.); Hospital Universitario La Paz-Instituto de Investigación del Hospital Universitario La Paz, Madrid (A.R.); L'Institut du Cancer de Montpellier-Val d'Aurelle, Montpellier (V.D.), Institut Bergonié, INSERM Unité 1312, and Université de Bordeaux UFR Sciences Médicales, Bordeaux (H.R.B.) - all in France; Providence Cancer Institute, Portland, OR (A.K.C.); the Department of Surgery, Oncology, and Gastroenterology, University of Padua, and Oncology 2, Istituto Oncologico Veneto IRCCS, Padua (V.G.), and the Cancer Center Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo (E.R.C.) - all in Italy; Stanford University School of Medicine, Stanford, CA (I.L.W.); the National Cancer Institute, Mexico City (C.A.-S.); Yale University School of Medicine, Yale Cancer Center, and Smilow Cancer Hospital, New Haven, CT (M.P.D.); the All-Ireland Cooperative Oncology Research Group (J.P.C.), and the Oncology Unit, Cancer Clinical Trials and Research Unit, Beaumont RCSI Cancer Centre, and Cancer Trials Ireland (B.T.H.) - all in Dublin; Fudan University Shanghai Cancer Center, Shanghai, China (Z.S.); Institute for Oncology and Radiology of Serbia, Belgrade (L.S.); Grupo Médico Ángeles, Guatemala City, Guatemala (H.C.-S.); Roche Products, Welwyn Garden City, United Kingdom (A.K., A.S.); and F. Hoffmann-La Roche, Basel, Switzerland (C.L., T.B., B.N., E.R.).
• N. Engl. J. Med. 2025 Jan 16; 392 (3): 249257249-257.

BackgroundPatients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer with residual invasive disease after neoadjuvant systemic therapy have a high risk of recurrence and death. The primary analysis of KATHERINE, a phase 3, open-label trial, showed that the risk of invasive breast cancer or death was 50% lower with adjuvant trastuzumab emtansine (T-DM1) than with trastuzumab alone.MethodsWe randomly assigned patients with HER2-positive early breast cancer with residual invasive disease in the breast or axilla after neoadjuvant systemic treatment with taxane-based chemotherapy and trastuzumab to receive T-DM1 or trastuzumab for 14 cycles. Here, we report the prespecified final analysis of invasive disease-free survival and the second interim analysis of overall survival.ResultsWith a median follow-up of 8.4 years, T-DM1 sustained the improvement in invasive disease-free survival over trastuzumab (unstratified hazard ratio for invasive disease or death, 0.54; 95% confidence interval [CI], 0.44 to 0.66). Seven-year invasive disease-free survival was 80.8% with T-DM1 and 67.1% with trastuzumab (difference, 13.7 percentage points). T-DM1 also led to a significantly lower risk of death than trastuzumab (unstratified hazard ratio, 0.66; 95% CI, 0.51 to 0.87; P = 0.003). Seven-year overall survival was 89.1% with T-DM1 and 84.4% with trastuzumab (difference, 4.7 percentage points). Adverse events of grade 3 or higher were noted in 26.1% of the patients in the T-DM1 group and 15.7% of those in the trastuzumab group.ConclusionsAs compared with trastuzumab, T-DM1 improved overall survival with sustained improvement in invasive disease-free survival among patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant therapy. (Funded by F. Hoffmann-La Roche/Genentech; KATHERINE ClinicalTrials.gov number, NCT01772472.).Copyright © 2025 Massachusetts Medical Society.

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