Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer
Mené sur 1 486 patientes atteintes d'un cancer du sein HER2+ de stade précoce avec maladie invasive résiduelle au niveau du sein ou des ganglions axillaires après un traitement systémique néoadjuvant comportant du trastuzumab et une chimiothérapie à base de taxane (durée médiane de suivi : 8,4 ans), cet essai randomisé de phase III évalue l'efficacité, du point de vue de la survie sans maladie invasive et la survie globale à 7 ans, et la toxicité d'un traitement adjuvant par trastuzumab emtansine (T-DM1)
Résumé en anglais
Background : Patients 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.
Methods : We 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.
Results : With 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.
Conclusions : As 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.)
