Final Analysis of the Phase III Multicentric Italian Study Short-HER: 9 Weeks Vs 1 Year Adjuvant Trastuzumab for HER2+ Early Breast Cancer

Introduction: chemotherapy plus 1 year trastuzumab is the standard adjuvant treatment for HER2+ breast cancer patients (pts). The Short-HER study is an independent, non-profit study aimed to test the non-inferiority of 9 weeks vs 1 year of adjuvant trastuzumab. Methods: HER2+ breast cancer pts were randomized to: Arm A (Long) AC or ECx4 followed by 4 courses of 3-weekly docetaxel in combination with trastuzumab, followed by 14 additional courses of 3-weekly trastuzumab; or Arm B (Short) 3 courses of 3-weekly docetaxel plus weekly trastuzumab for 9 doses followed by FEC x3. When indicated, radiation therapy and hormone therapy were started after the completion of chemotherapy. ShortHER is a non-inferiority trial with disease-free survival (DFS) as primary end-point. The sample size of 1250 pts has been estimated on the basis of an hazard ratio <1.29 for the short arm to be non-inferior. The definitive analysis was planned after 198 DFS events or a 5yr median follow up. Hazard ratio for DFS and OS (90% CI) are estimated according to the Cox model; data are also analyzed by the Bayesian approach. Results: from Dec-2007 to Oct-2013, 1254 pts from 82 centers have been randomized. Pts characteristics are: median age 55 yrs (25-78); pts older than 60 yr 36%; stage I 40.6%, II 43.8%, stage III 15.2%; N0 53.5%, 1-3 positive nodes 30.7%, ≥ 4 15.2%. Sixty-eight% of the pts had ER+ tumors. Characteristics were balanced between the two arms. At the time of the analysis, 189 events have occurred and the median follow up of the study is 5.2 yrs. A total of 109 Grade ≥ 2 cardiac events have been reported, 82 in arm A (long) and 27 in arm B (short) (p < 0.0001); grade 3-4 cardiac events were 13 in arm A and 5 in arm B. Conclusions: Shorter trastuzumab administration significantly reduces the rate of severe cardiac toxicity. Final DFS data will be reported at the time of the meeting. EudraCT: 2007-004326-25.