TY - JOUR
T1 - Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D)
AU - Moreno-Aspitia, Alvaro
AU - Holmes, Eileen M.
AU - Jackisch, Christian
AU - de Azambuja, Evandro
AU - Boyle, Frances
AU - Hillman, David W.
AU - Korde, Larissa
AU - Fumagalli, Debora
AU - Izquierdo, Miguel A.
AU - McCullough, Ann E.
AU - Wolff, Antonio C.
AU - Pritchard, Kathleen I.
AU - Untch, Michael
AU - Guillaume, Sébastien
AU - Ewer, Michael S.
AU - Shao, Zhimin
AU - Sim, Sung Hoon
AU - Aziz, Zeba
AU - Demetriou, Georgia
AU - Mehta, Ajay O.
AU - Andersson, Michael
AU - Toi, Masakazu
AU - Lang, Istvan
AU - Xu, Binghe
AU - Smith, Ian E.
AU - Barrios, Carlos H.
AU - Baselga, Jose
AU - Gelber, Richard D.
AU - Piccart-Gebhart, Martine
AU - ALTTO Steering Committee and Investigators
AU - Hilbers, Florentine
AU - El-Abed, Sarra
AU - Balta, Vasiliki
AU - Schurmans, Celine
AU - Rosa, Daniela D.
AU - Saini, Kamal
AU - Filho, Otto Metzger
AU - McConnell, Robin
AU - Paterson, Vicki
AU - Campbell, Christine
AU - McFadden, Eleanor
AU - Paterson, Emma
AU - Kassab, Garrick
N1 - Funding Information:
Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers U10CA180821 and U10CA180882 (to the Alliance for Clinical Trials in Oncology), UG1CA233180 , UG1CA233196 , UG1CA233329 , UG1CA232760 ; U10CA180863 to the Canadian Clinical Trials Group and grant 704970 from the Canadian Cancer Society; GlaxoSmithKline from its initial development until 30th November 2015, and Novartis since December 2015. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. https://acknowledgments.alliancefound.org/ .
Funding Information:
The ALTTO trial ( NCT00490139 ) is a prospective randomised, phase 3, open-label, multicenter study conducted in 946 centers in 44 countries from 4 different continents. The patients were enrolled between June 2007 and July 2011. Participating medical centers’ institutional review boards (or Ethics Committees) approved the study, and all patients provided written informed consent prior to study entry. The trial was coordinated by the Breast International Group (BIG) for Europe and the rest of the world and by the North Central Cancer Treatment Group (NCCTG: now Alliance) for the United States of America and Canada. Support was provided by the US National Cancer Institute (NCI), National Cancer Institute of Canada Clinical Trials Group (now Canadian Clinical Trials Group), Glaxo-Smith-Kline from its development until 30th November 2015 and by Novartis since then. The clinical database was located at the BrEAST Data Center (Institut Jules Bordet, Brussels), and statistical analyses were performed by Frontier Science Scotland (FSS, Scotland).
Publisher Copyright:
© 2021 Elsevier Ltd
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/5
Y1 - 2021/5
N2 - Aim: To present the pre-specified analyses of >5-years follow-up of the Phase III ALTTO trial.Patients and methods: 8381 patients with stage I-III HER2 positive breast cancer randomised to chemotherapy plus 1-year of trastuzumab (T), oral lapatinib (L; no longer evaluated), trastuzumab followed by lapatinib (T→L), and lapatinib + trastuzumab (L+T). The primary endpoint was disease-free survival (DFS). A secondary analysis examined DFS treatment effects by hormone receptor status, nodal status and chemotherapy timing; time to recurrence; overall survival (OS) and safety (overall and cardiac).Results: At a median follow-up of 6.9 years, 705 DFS events for L+T versus T were observed. Hazard Ratio (HR) for DFS was 0.86 (95% CI, 0.74–1.00) for L+T versus T and 0.93 (95% CI, 0.81–1.08) for T→L versus T. The 6-year DFS were 85%, 84%, and 82% for L+T, T→L, and T, respectively. HR for OS was 0.86 (95% CI, 0.70–1.06) for L+T versus T and 0.88 (95% CI, 0.71–1.08) for T→L versus T. The 6-year OS were 93%, 92%, and 91% for L+T, T→L, and T, respectively. Subset analyses showed a numerically better HR for DFS in favour of L+T versus T for the hormone-receptor-negative [HR 0.80 (95% CI, 0.64–1.00; 6-yr DFS% = 84% versus 80%)] and the sequential chemotherapy [HR 0.83 (95% CI, 0.69–1.00; 6-yr DFS% = 83% versus79%)] subgroups.Conclusion: T+L did not significantly improve DFS and OS over T alone, both with chemotherapy, and, therefore, cannot be recommended for adjuvant treatment of early-stage HER2-positive breast cancer.Trial Registration: clinicaltrials.gov Identifier NCT00490139.
AB - Aim: To present the pre-specified analyses of >5-years follow-up of the Phase III ALTTO trial.Patients and methods: 8381 patients with stage I-III HER2 positive breast cancer randomised to chemotherapy plus 1-year of trastuzumab (T), oral lapatinib (L; no longer evaluated), trastuzumab followed by lapatinib (T→L), and lapatinib + trastuzumab (L+T). The primary endpoint was disease-free survival (DFS). A secondary analysis examined DFS treatment effects by hormone receptor status, nodal status and chemotherapy timing; time to recurrence; overall survival (OS) and safety (overall and cardiac).Results: At a median follow-up of 6.9 years, 705 DFS events for L+T versus T were observed. Hazard Ratio (HR) for DFS was 0.86 (95% CI, 0.74–1.00) for L+T versus T and 0.93 (95% CI, 0.81–1.08) for T→L versus T. The 6-year DFS were 85%, 84%, and 82% for L+T, T→L, and T, respectively. HR for OS was 0.86 (95% CI, 0.70–1.06) for L+T versus T and 0.88 (95% CI, 0.71–1.08) for T→L versus T. The 6-year OS were 93%, 92%, and 91% for L+T, T→L, and T, respectively. Subset analyses showed a numerically better HR for DFS in favour of L+T versus T for the hormone-receptor-negative [HR 0.80 (95% CI, 0.64–1.00; 6-yr DFS% = 84% versus 80%)] and the sequential chemotherapy [HR 0.83 (95% CI, 0.69–1.00; 6-yr DFS% = 83% versus79%)] subgroups.Conclusion: T+L did not significantly improve DFS and OS over T alone, both with chemotherapy, and, therefore, cannot be recommended for adjuvant treatment of early-stage HER2-positive breast cancer.Trial Registration: clinicaltrials.gov Identifier NCT00490139.
KW - Adjuvant chemotherapy
KW - Early breast cancer
KW - HER2
KW - Lapatinib
KW - Trastuzumab
UR - http://www.scopus.com/inward/record.url?scp=85102857093&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2021.01.053
DO - 10.1016/j.ejca.2021.01.053
M3 - Article
C2 - 33765513
AN - SCOPUS:85102857093
SN - 0959-8049
VL - 148
SP - 287
EP - 296
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -