TY - JOUR
T1 - Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D)
AU - for the ALTTO Steering Committee and Investigators
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 - 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 - Publisher Copyright:
© 2021 Elsevier Ltd
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
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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 -