• Jens Huober, Eileen Holmes, José Baselga, Evandro de Azambuja, Michael Untch, Debora Fumagalli, Severine Sarp, Istvan Lang, Ian Smith, Frances Boyle, Binghe Xu, Christophe Lecocq, Hans Wildiers, Christelle Jouannaud, John Hackman, Lokanatha Dasappa, Eva Ciruelos, Juan Carlos Toral Pena, Hryhoriy Adamchuk, Tamas Hickish, Lorena de la Pena, Christian Jackisch, Richard D Gelber, Martine Piccart-Gebhart, and Serena Di Cosimo.
• University of Ulm, Breast Center, Ulm, Germany. Electronic address: jens.huober@uniklinik-ulm.de.
• Eur. J. Cancer. 2019 Sep 1; 118: 169-177.

BackgroundLapatinib (L) plus trastuzumab (T) with weekly paclitaxel significantly increased the pathologic complete response (pCR) rate compared with the anti-human epidermal growth factor receptor 2 (HER2) agent alone plus paclitaxel. The event-free survival (EFS) and overall survival (OS) by the treatment arms L + T vs. T and L vs. T and the relationship between pCR and EFS/OS both in the whole study population and according to hormone receptor-negative and hormone receptor-positive cohorts after a median follow-up of 6.7 years were assessed.Patients And MethodsFour hundred fifty-five patients with HER2-positive early breast cancer randomly received L 1500 mg/day (n = 154), T (common dose, n = 149) or L 1000 mg/day plus T (n = 152) for 6 weeks, followed by the assigned anti-HER2 treatment combined with paclitaxel weekly × 12. After surgery, patients received 3 cycles of fluorouracil, epirubicin and cyclophosphamide. The primary end-point was pCR (ypT0/is; for current analysis, it is ypT0/is ypN0), and the secondary end-points were EFS and OS.ResultsSix-year EFS rates were 67%, 67% and 74% with L, T and L + T, respectively (L vs T: hazard ratio [HR], 0.98 [95% confidence interval {CI}, 0.64-1.51; P = .93]; L + T vs T: HR, 0.81 [95% CI, 0.52-1.26; P = .35]). Six-Year OS rates were 82%, 79% and 85% for L, T and L + T, respectively (L vs T: HR, 0.85 [95% CI, 0.49-1.46; P = .56]; L + T vs T: HR, 0.72 [95% CI, 0.41-1.27; P = .26]). In landmark analyses, patients with a pCR had a significantly higher 6-year EFS (77% and 65%) and OS (89% and 77%) compared with those without a pCR for both overall and the hormone receptor-negative cohort.ConclusionAchieving a pCR is important in HER2-positive disease and translates into better long-term outcome with regard to EFS and OS.Copyright © 2019 Elsevier Ltd. All rights reserved.

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