9 weeks vs 1 year adjuvant trastuzumab in combination with chemotherapy: final results of the phase III randomized Short-HER study
Mené sur 1 254 patientes atteintes d'un cancer du sein HER2+, cet essai de phase III évalue la non-infériorité, du point de vue de la survie sans maladie, et la toxicité d'une administration de courte durée du trastuzumab (9 semaines), dispensé en traitement adjuvant avec une chimiothérapie, en comparaison avec une administration longue (1 an)
Background : Chemotherapy plus 1-year trastuzumab is the standard adjuvant treatment for 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 vs 1 year of adjuvant trastuzumab combined with chemotherapy. Patients and methods : HER2-positive breast cancer patients with node-positive or, if node negative, with at least one risk factor (pT > 2cm, 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 endpoints included 2-year failure rate and cardiac safety. Results : 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 was 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-yr OS is 95.2% in the long and 95.0% in the short arm (HR 1.07, 90%CI0.74;1.56). Cardiac events are significantly lower in the short arm (risk-ratio 0.33, 95%CI0.22;0.50, p < 0.0001). Conclusions : This study failed to show the non-inferiority of a shorter trastuzumab administration. 1-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.
Annals of Oncology 2018