Tolerability and toxicity of trastuzumab or trastuzumab plus lapatinib in older patients: a sub-analysis of the ALTTO trial (BIG 2-06; NCCTG (Alliance) N063D)

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.

Automated summary

In the study, older patients (>=65 years old) using trastuzumab plus lapatinib had worse treatment completion outcomes and toxicity compared to younger patients. However, trastuzumab was generally well tolerated among older patients. Older patients presented with a higher number of comorbidities at randomization.