Final analysis of the ALTTO trial: adjuvant trastuzumab in sequence or in combination with lapatinib in patients with HER2-positive early breast cancer [BIG 2-06/NCCTG N063D (Alliance)]

• Published in: ESMO open Vol. 9; no. 11; p. 103938
• Main Authors: de Azambuja, E., Piccart-Gebhart, M., Fielding, S., Townend, J., Hillman, D.W., Colleoni, M., Roylance, R., Kelly, C.M., Lombard, J., El-Abed, S., Choudhury, A., Korde, L., Vicente, M., Chumsri, S., Rodeheffer, R., Ellard, S.L., Wolff, A.C., Holtschmidt, J., Lang, I., Untch, M., Boyle, F., Xu, B., Werutsky, G., Tujakowski, J., Huang, C.-S., Baruch, N.B., Bliss, J., Ferro, A., Gralow, J., Kim, S.-B., Kroep, J.R., Krop, I., Kuemmel, S., McConnell, R., Moscetti, L., Knop, A.S., van Duijnhoven, F., Gomez, H., Cameron, D., Di Cosimo, S., Gelber, R.D., Moreno-Aspitia, A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-11-2024; Elsevier
• Subjects: adjuvant chemotherapy; early breast cancer; HER2-positive; lapatinib; Original Research; trastuzumab; early breast cancer; trastuzumab; lapatinib; adjuvant chemotherapy; HER2-positive
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1016/j.esmoop.2024.103938

Dual anti-human epidermal growth factor receptor 2 (HER2) blockade has improved the outcomes of patients with early and metastatic HER2-positive breast cancer. Here we present the final 10-year analysis of the ALTTO trial.
The ALTTO trial (NCT00490139) is a prospective randomized, phase III, open-label, multicenter study that investigated the role of adjuvant chemotherapy and trastuzumab alone, in combination or sequentially with lapatinib. The primary endpoint was disease-free survival (DFS) and secondary endpoints included overall survival (OS), time to distant recurrence and safety.
Overall, 6281 patients with HER2-positive early breast cancer were included in the final efficacy analysis in three treatment groups: trastuzumab (T), lapatinib + trastuzumab (L + T) and trastuzumab followed by lapatinib (T→L). Baseline characteristics were well balanced between groups. At a median follow-up of 9.8 years, the addition of lapatinib to trastuzumab and chemotherapy did not significantly improve DFS nor OS. The 10-year DFS was 77% in T, 79% in L + T and 79% in T→L, and the 10-year OS was 87%, 89% and 89%, respectively. The incidence of any cardiac event was low and similar in the three treatment groups.
With a longer follow-up, no significant improvement was observed in DFS in patients treated with dual anti-HER2 blockade with lapatinib + trastuzumab compared to trastuzumab alone. The 10-year survival rates for the combination group are consistent with other studies that have explored dual anti-HER2 therapy.
•Dual anti-HER2 therapy with L + T did not improve DFS compared to trastuzumab alone in ALTTO.•Ten-year OS rates were similar: 87% in trastuzumab, 89% in L + T and 89% in T→L treatment groups.•Central nervous system recurrence as the first site of relapse was consistently 2% across all treatment groups.•Cardiac event rates were low, with fewer events in the L and T→L groups compared to trastuzumab alone.•Higher treatment interruptions and dose delays were observed in dual anti-HER2 therapy groups compared to trastuzumab alone.