• P Conte, A Frassoldati, G Bisagni, A A Brandes, M Donadio, O Garrone, F Piacentini, L Cavanna, F Giotta, M Aieta, V Gebbia, A Molino, A Musolino, A Ferro, R Maltoni, S Danese, C Zamagni, A Rimanti, K Cagossi, A Russo, P Pronzato, F Giovanardi, G Moretti, L Lombardo, A Schirone, A Beano, L Amaducci, E A Bajardi, R Vicini, S Balduzzi, R D'Amico, and V Guarneri.
• Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy; Medical Oncology 2, Istituto Oncologico Veneto (IOV), IRCCS, Padova, Italy. Electronic address: pierfranco.conte@unipd.it.
• Ann. Oncol. 2018 Dec 1; 29 (12): 2328-2333.

BackgroundChemotherapy plus 1-year trastuzumab is the standard adjuvant treatment of HER2-positive breast cancer. The efficacy of less extended trastuzumab exposure is under investigation. The short-HER study was aimed to assess the non-inferiority of 9 weeks versus 1 year of adjuvant trastuzumab combined with chemotherapy.Patients And MethodsHER2-positive breast cancer patients with node-positive or, if node negative, with at least one risk factor (pT>2 cm, G3, lympho-vascular invasion, Ki-67 > 20%, age ≤35 years, or hormone receptor negativity) were randomly assigned to receive sequential anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or plus 9 weeks trastuzumab (arm B, short). This study was designed as a non-inferiority trial with disease-free survival (DFS) as primary end point. A DFS hazard ratio (HR) <1.29 was chosen as the non-inferiority margin. Analyses according to the frequentist and Bayesian approach were planned. Secondary end points included 2-year failure rate and cardiac safety.ResultsA total of 1254 patients from 82 centers were randomized (arm A, long: n = 627; arm B, short: n = 626). Five-year DFS is 88% in the long and 85% in the short arm. The HR is 1.13 (90% CI 0.89-1.42), with the upper limit of the CI crossing the non-inferiority margin. According to the Bayesian analysis, the probability that the short arm is non-inferior to the long one is 80%. The 5-year overall survival (OS) is 95.2% in the long and 95.0% in the short arm (HR 1.07, 90% CI 0.74-1.56). Cardiac events are significantly lower in the short arm (risk-ratio 0.33, 95% CI 0.22-0.50, P < 0.0001).ConclusionsThis study failed to show the non-inferiority of a shorter trastuzumab administration. One-year trastuzumab remains the standard. However, a 9-week administration decreases the risk of severe cardiac toxicity and can be an option for patients with cardiac events during treatment and for those with a low risk of relapse.Trial RegistrationEUDRACT number: 2007-004326-25; NCI ClinicalTrials.gov number: NCT00629278.

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