Effect of early adverse events resulting in ado-trastuzumab emtansine dose adjustments on survival outcomes of HER2+ advanced breast cancer patients.

ABSTRACT

PURPOSE: Ado-trastuzumab emtansine (T-DM1) treatment in HER2+ advanced breast cancer patients is generally well tolerated, but when adverse events occur dose adjustments may be required. This study evaluated the impact of early adverse events requiring T-DM1 dose interruptions or reductions on overall survival (OS) and progression-free survival (PFS) in HER2+ advanced metastatic breast cancer patients in the clinical trials EMILIA and TH3RESA. PATIENTS AND METHODS: The study included 893 participants initiated on T-DM1 treatment. A landmark approach set at 4 months was used to evaluate the association between early adverse events requiring T-DM1 dose interruptions or reductions and OS/PFS. Cox proportional hazard analysis modeled the association between events requiring T-DM1 dose interruptions or reductions and OS/PFS. Associations were reported as hazard ratios with 95% confidence intervals. RESULTS: Adverse events requiring T-DM1 dose interruptions or reductions within the first 4 months of treatment were not significantly associated with OS (hazard ratio (HR) [95% CI] dose interrupted = 1.15 [0.85-1.55]; dose reduced = 0.75 [0.49-1.14]; P = 0.214) nor PFS (hazard ratio (HR) [95% CI] dose interrupted = 1.13 [0.87-1.48]; dose reduced = 0.90 [0.62-1.31]; P = 0.534). CONCLUSION: The occurrence of early adverse events requiring T-DM1 dose interruptions or reductions do not appear to be associated with altered long-term OS or PFS within a pooled analysis of data from EMILIA and TH3RESA.