Abstract
Purpose
Little is known about the use of trastuzumab or trastuzumab + lapatinib in older patients. We have performed a sub-analysis of the Adjuvant Lapatinib And/Or Trastuzumab Treatment Optimisation (ALTTO) trial focused on toxicity and treatment completion of both regimens in older patients (≥ 65 years old)
Methods
The ALTTO trial randomised 8381 patients with early HER2-positive BC in 4 arms. Eligible patients for this study were those having received at least one dose of assigned treatment in either the trastuzumab or trastuzumab + lapatinib arms. Treatment completion was evaluated through the rate of temporary treatment interruptions, permanent treatment discontinuations and lapatinib dose reductions. Toxicity was evaluated via a selected subset of adverse events of interest (AEI). Risk factors for both treatment completion outcomes and toxicity were investigated, including comorbidities and use of 5 or more co-medications at randomization.
Results
A total of 430 patients ≥ 65 year were eligible. Median age was 68 (range 65–80). In comparison with the younger cohort, older patients had a significantly higher number of comorbidities at randomization (p < 0.001). Treatment completion outcomes were worse, particularly in the trastuzumab + lapatinib arm. Adverse events of interest were likewise more common in the trastuzumab + lapatinib arm with higher AEI rates (63.4% in younger vs 78.0% in older, p < 0.001). Concomitant chemotherapy was associated with worse treatment completion outcomes among older patients.
Conclusion
Trastuzumab plus lapatinib was significantly more toxic among older patients and had worse treatment completion. Trastuzumab was generally well tolerated.
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Change history
08 October 2021
A Correction to this paper has been published: https://doi.org/10.1007/s10549-021-06409-y
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Funding
The ALTTO Trial, as well as this subanalysis, has been funded by GSK and Novartis.
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Dr Noam Pondé reports he has received fees from Novartis, Lilly, AstraZeneca and Roche. He has received travel grants from Novartis, AstraZeneca and Lilly. Florentine Hilbers reports that her institution has received research grants to fund the ALTTO trial from GSK and Novartis. Christian Jackisch reports grants and fees from Roche, Novartis, and AstraZeneca. Olena Werner is an employee of Novartis. Dr. Richard D. Gelber reports that his institution received grants for partial support for his salary from Novartis, Roche, Merck, Pfizer, AstraZeneca, Celgene, Ipsen, and Ferring. Evandro de Azambuja reports honoraria and advisory board from Roche/GNE, Novartis and SeaGen, travel grants from Roche/GNE and GSK/Novartis and research grant to my institution from Roche/GNE, Astra-Zeneca, GSK/Novartis and Servier. Martine Piccart is a board member for Oncolytics and Radius. She has received honoraria from AstraZeneca, Camel-IDS, Crescendo Biologics, Debiopharm, G1 Therapeutics, Genentech, Huya, Immunomedics, Lilly, Menarini, MSD, Novartis, Odonate, Oncolytics, Periphagen, Pfizer, Roche PharmaMar, and Seattle Genetics. Her institute has received research grants from AstraZeneca, Lilly, MSD, Novartis, Pfizer, Radius, Roche-Genentech, Servier and Synthon. Dominique Agbor-Tarh, Lissandra Dal Lago, Larissa A. Korde, Aminah Jatoi, Amylou C. Dueck, Alvaro Moreno-Aspitia and Christos Sotiriou report no conflicts of interest.
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Pondé, N., Agbor-Tarh, D., Dal Lago, L. et al. Tolerability and toxicity of trastuzumab or trastuzumab + lapatinib in older patients: a sub-analysis of the ALTTO trial (BIG 2-06; NCCTG (Alliance) N063D). Breast Cancer Res Treat 185, 107–116 (2021). https://doi.org/10.1007/s10549-020-05915-9
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DOI: https://doi.org/10.1007/s10549-020-05915-9