Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D)
Alvaro Moreno-Aspitia, Eileen M Holmes, Christian Jackisch, Evandro de Azambuja, Frances Boyle, David W Hillman, Larissa Korde, Debora Fumagalli, Miguel A Izquierdo, Ann E McCullough, Antonio C Wolff, Kathleen I Pritchard, Michael Untch, Sébastien Guillaume, Michael S Ewer, Zhimin Shao, Sung Hoon Sim, Zeba Aziz, Georgia Demetriou, Ajay O Mehta, Michael Andersson, Masakazu Toi, Istvan Lang, Binghe Xu, Ian E Smith, Carlos H Barrios, Jose Baselga, Richard D Gelber, Martine Piccart-Gebhart, ALTTO Steering Committee and Investigators, Florentine Hilbers, Sarra El-Abed, Vasiliki Balta, Celine Schurmans, Daniela D Rosa, Kamal Saini, Otto Metzger Filho, Robin McConnell, Vicki Paterson, Christine Campbell, Eleanor McFadden, Emma Paterson, Garrick Kassab, Alvaro Moreno-Aspitia, Eileen M Holmes, Christian Jackisch, Evandro de Azambuja, Frances Boyle, David W Hillman, Larissa Korde, Debora Fumagalli, Miguel A Izquierdo, Ann E McCullough, Antonio C Wolff, Kathleen I Pritchard, Michael Untch, Sébastien Guillaume, Michael S Ewer, Zhimin Shao, Sung Hoon Sim, Zeba Aziz, Georgia Demetriou, Ajay O Mehta, Michael Andersson, Masakazu Toi, Istvan Lang, Binghe Xu, Ian E Smith, Carlos H Barrios, Jose Baselga, Richard D Gelber, Martine Piccart-Gebhart, ALTTO Steering Committee and Investigators, Florentine Hilbers, Sarra El-Abed, Vasiliki Balta, Celine Schurmans, Daniela D Rosa, Kamal Saini, Otto Metzger Filho, Robin McConnell, Vicki Paterson, Christine Campbell, Eleanor McFadden, Emma Paterson, Garrick Kassab
Abstract
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.
Keywords: Adjuvant chemotherapy; Early breast cancer; HER2; Lapatinib; Trastuzumab.
Conflict of interest statement
Conflict of interest statement The authors declare the following financial interests/personal relationships that may be considered as potential competing interests:
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Source: PubMed