First results from the phase III ALTTO trial (BIG 2-06; NCCTG [Alliance] N063D) comparing one year of anti-HER2 therapy with lapatinib alone (L), trastuzumab alone (T), their sequence (T→L), or their combination (T+L) in the adjuvant treatment of HER2-positive early breast cancer (EBC).

Breast Cancer - HER2/ER
Session Type and Session Title: 
Plenary Session, Plenary Session Including the Science of Oncology Award and Lecture
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr LBA4)
Martine J. Piccart-Gebhart, Andrew Peter Holmes, Jose Baselga, Evandro De Azambuja, Amylou C. Dueck, Giuseppe Viale, Jo Anne Zujewski, Aron Goldhirsch, Sergio Santillana, Kathleen I. Pritchard, Antonio C. Wolff, Christian Jackisch, Istvan Lang, Michael Untch, Ian E. Smith, Frances Boyle, Binghe Xu, Henry Leonidas Gomez, Richard D. Gelber, Edith A. Perez; Jules Bordet Institute, Breast International Group, Brussels, Belgium; Frontier Science Scotland Ltd, Kincraig, United Kingdom; Memorial Sloan Kettering Cancer Center, New York, NY; Institut Jules Bordet, Brussels, Université Libre de Bruxelles, Brussels, Belgium; Mayo Clinic, Scottsdale, AZ; Division of Pathology, European Institute of Oncology, Milan, Italy; National Cancer Institute, Bethesda, MD; Division of Medical Oncology, European Institute of Oncology, Milan, Italy; GlaxoSmithKline, Malvern, PA; Sunnybrook Odette Cancer Centre and the University of Toronto, Toronto, ON, Canada; The Johns Hopkins Hospital and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Sana Kliniken Offenbach, Offenbach, Germany; Országos Onkológiai Intézet, Budapest, Hungary; Helios Klinikum Berlin-Buch, Berlin, Germany; The Royal Marsden NHS Foundation Trust, London, United Kingdom; Patricia Ritchie Centre for Cancer Care and Research, The University of Sydney, Mater Hospital, Sydney, Australia; Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China; Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA; Mayo Clinic, Jacksonville, FL

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Abstract Disclosures


Background: Lapatinib (L) is a HER1-HER2 tyrosine kinase inhibitor. The Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALTTO) Trial is a randomised, phase III trial comparing 3 oral L-containing regimens with T, each given for 1 year. Methods: From June 2007 to July 2011, 8381 patients (pts) were randomised from 946 sites in 44 countries to receive either L+T, T→L, L, or T. Anti-HER2 therapy was initiated after completing all chemotherapy (N=4613), concurrently with a taxane following anthracycline (N=3337), or concurrently with a non-anthracycline, platinum-containing regimen (N=431). The L arm was closed in Aug 2011 for futility and is not presented. The primary endpoint is invasive disease-free survival (DFS). L+T vs. T is tested for superiority and T→L vs. T is tested for non-inferiority at 1.11 margin. P≤0.025 is required for statistical significance. 850 DFS events in the L+T vs. T comparison would provide 80% power to detect a true hazard ratio (HR) of 0.80 with experiment-wide alpha=0.05. The current analysis was planned to occur either after observing these 850 events or at 4.5 yrs median follow up (MFU). Results: Pt and disease characteristics were well balanced. 40% were node-negative and 57% were hormone receptor positive. Only 555 DFS events for the L+T vs. T comparison were observed at 4.5 years MFU. HR for DFS was 0.84 (97.5% CI, 0.70-1.02; P=0.048; 4-yr DFS%=88% vs. 86%) for L+T vs. T and 0.93 (97.5% CI, 0.76-1.13; non-inferiority P=0.044; 4-yr DFS%=87% vs. 86%) for T→L vs. T. Diarrhoea (75% vs. 20%), rash (55% vs. 20%) and hepatobiliary (23% vs. 16%) adverse events were more frequent in L+T vs. T. Primary cardiac endpoints were infrequent (<1%) in all arms. Conclusions: L+T has lower risk of a DFS event compared with T, and T→L appeared non-inferior to T, but neither finding was statistically significant. The first DFS results of dual HER2 blockade in the adjuvant ALTTO at 4.5 years MFU are unexpected considering the effect shown by doubling the pCR rate with L+T vs. T in the NeoALLTO trial. Follow up continues. Clinical trial information: NCT00490139.