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

  • Ethan TangEmail author
  • Andrew Rowland
  • Ross A. McKinnon
  • Michael J. Sorich
  • Ashley M. Hopkins
Brief Report

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.

Keywords

Ado-trastuzumab emtansine Adverse events Dose adjustment Survival Advanced breast cancer 

Notes

Acknowledgements

Research undertaken with the financial support of Cancer Council South Australia’s Beat Cancer Project on behalf of its donors and the State Government through the Department of Health (Grant ID: 1159924 and 1127220). Ashley M. Hopkins is an early career researcher funded by a Fellowship from the National Breast Cancer Foundation, Australia (PF-17-007). Ross A. McKinnon is supported by the Cancer Council’s Beat Cancer Project with support from the South Australian Department of Health.

Author contribution

All authors were involved in literature search, design, analysis, interpretation and manuscript preparation for this project.

Compliance with ethical standards

Conflict of interest

Michael J. Sorich and Andrew Rowland report investigator-initiated project grants from Pfizer, outside the scope of the submitted work. Ashley M. Hopkins, Ethan Tang, Ross A. McKinnon have no conflicts of interest to disclose.

Ethical approval

Secondary analysis of anonymized participant-level trial data was approved by Southern Adelaide Clinical Human Research Ethics Committee.

Supplementary material

10549_2019_5393_MOESM1_ESM.docx (16 kb)
Supplementary material 1 (DOCX 16 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.College of Medicine and Public HealthFlinders UniversityAdelaideAustralia
  2. 2.Flinders Medical CentreBedford ParkAustralia

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