Follow-up results of NOAH, a randomized phase III trial evaluating neoadjuvant chemotherapy with trastuzumab (CT+H) followed by adjuvant H versus CT alone, in patients with HER2-positive locally advanced breast cancer.

Breast Cancer - HER2/ER
Session Type and Session Title: 
Oral Abstract Session, Breast Cancer - HER2/ER
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 503)
Luca Gianni, Wolfgang Eiermann, Vladimir Semiglazov, Alexey Manikhas, Ana Lluch, Sergei Tjulandin, Milvia Zambetti, Federico Vazquez, Mikhail J. Byakhov, Mikhail Lichinitser, Miguel Angel Climent, Eva Ciruelos, Belen Ojeda, Mauro Mansutti, Alla Bozhok, Domenico Magazzu, Jutta Steinseifer, Pinuccia Valagussa, Jose Baselga; San Raffaele Hospital, Milan, Italy; Interdisziplinäres Onkologisches Zentrum München, Munich, Germany; N. N. Petrov Research Institute of Oncology, St. Petersburg, Russia; City Clinical Oncological Dispensary, St. Petersburg, Russia; Hospital Clínico Universitario de Valencia- INCLIVA Health Research Institute, University of Valencia, Valencia, Spain; Russian Oncology Research Center; N.N. Blokhin Cancer Research Center, Moscow, Russia; Vall d'Hebron University Hospital, Barcelona, Spain; Central Clinical Hospital named N.A.Semashko, Moscow, Russia; N.N. Blokhin Russian Cancer Research Center, Moscow, Russia; Instituto Valenciano de Oncologia, Valencia, Spain; University Hospital 12 de Octubre, Madrid, Spain; Hospital de la Santa Creu i Sant Pau, Departement of Medical Oncology, Barcelona, Spain; Department of Oncology, University Hospital of Udine, Udine, Italy; N.N. Petrov Research Institute of Oncology, St. Petersburg, Russia; Fondazione Michelangelo, Milan, Italy; F. Hoffmann-La Roche Ltd, Basel, Switzerland; Memorial Sloan-Kettering Cancer Center, New York, NY

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Abstract Disclosures


Background: The monoclonal antibody trastuzumab (H) has been shown to improve event-free survival (EFS) and pathologic complete response (pCR) in patients with HER2-positive locally advanced or inflammatory breast cancer receiving neoadjuvant chemotherapy with or without one year of trastuzumab in the primary analysis of the NOAH study (Gianni L, Lancet 2010). Updated EFS and overall survival (OS) results are now presented. Methods: In this international, multicenter, open-label, randomized phase III trial patients with locally advanced or inflammatory breast cancer were randomized 1:1 to receive CT+H followed by adjuvant H versus CT alone. A parallel cohort of 99 comparable patients with HER2-negative disease was included and treated with the same chemotherapy regimen. The neoadjuvant chemotherapy regimen included doxorubicin, paclitaxel, cyclophosphamide, methotrexate and 5-fluorouracil. The primary objective was to compare EFS defined as time from randomization to disease recurrence or progression [local, regional, distant or contralateral] or death due to any cause). Results: After a median follow up of 5.4 years, the EFS benefit with trastuzumab was confirmed. Cardiac tolerability was good despite concurrent administration of trastuzumab with doxorubicin. Two patients (2%) developed reversible symptomatic congestive heart failure and are presently alive. Conclusions: Present analysis confirms the significant EFS benefit observed in the primary analysis of the NOAH study, and shows a strong trend towards improved OS with the addition of trastuzumab to chemotherapy. pCR rate may be considered as a possible primary endpoint and early indicator of benefit in future neoadjuvant studies of HER2-targeted agents. Clinical trial information: 86043495.

Parameter HER2-positive HER2-negative
CT alone
p value
5-yr EFS (%) 57.5 43.3 0.64, 0.016 60.5
5-yr EFS in pCR (%) 86.5 54.8 0.29, 0.008 85.9
5-yr OS (%) 73.5 62.9 0.66, 0.055 76.4
5-yr BCSS (%) 77.4 63.9 0.59, 0.023 78.6

Abbreviations: EFS, event free survival; OS, overall survival; BCSS, breast cancer specific survival; HR, hazard ratio.