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Effect of early adverse events resulting in sorafenib dose adjustments on survival outcomes of advanced hepatocellular carcinoma patients

Abstract

Background

Sorafenib is a current first-line treatment option for advanced hepatocellular carcinoma (HCC). This study aimed to evaluate the impact of early adverse events (AEs) requiring sorafenib dose adjustment on survival outcomes of patients with advanced HCC.

Methods

The study was a secondary analysis of the phase III clinical trial NCT00699374. A landmark Cox proportional hazard analysis was used to evaluate the association between early AEs requiring sorafenib dose adjustment with survival outcomes. The primary outcome was overall survival (OS) with progression-free survival (PFS) as secondary.

Results

AEs requiring sorafenib dose adjustment within the first 28 days of therapy were significantly associated with OS (HR [95% CI]; dose interruption = 0.9 [0.7–1.2]; dose reduction = 0.6 [0.5–0.9]; discontinuation = 1.7 [0.9–3.4]; P = 0.005). No statistically significant association with PFS was identified (P = 0.148).

Conclusion

Sorafenib dose interruptions and reduction due to AEs did not compromise the survival outcomes of patient with advanced HCC. Patients who required a sorafenib dose reduction were observed to have more favourable OS compared to those who did not experience an AE which required a dose adjustment.

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Acknowledgements

This publication uses information obtained from https://www.projectdatasphere.org, which is maintained by Project Data Sphere, LLC. Neither Project Data Sphere, LLC nor the owners of any information from the web site have contributed to, approved or are in any way responsible for the contents of this publication.

Funding

Ashley Hopkins is an early career researcher funded by a Fellowship from the National Breast Cancer Foundation, Australia. Warit Ruanglertboon was supported by the Royal Thai Government Scholarship, Thailand. Andrew Rowland (mid-career) and Michael Sorich (principal) are funded by a Beat Cancer Fellowships from Cancer Council of South Australia, Australia. 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).

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All authors contributed to study design, interpretation, and preparation the manuscript.

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Correspondence to Warit Ruanglertboon.

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Conflict of interest

M. J. S. and A. R. report investigator-initiated project grants from Pfizer, outside the scope of the submitted work. A. M. H. and W. R. have no conflicts of interest to disclose.

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Ruanglertboon, W., Sorich, M.J., Rowland, A. et al. Effect of early adverse events resulting in sorafenib dose adjustments on survival outcomes of advanced hepatocellular carcinoma patients. Int J Clin Oncol 25, 1672–1677 (2020). https://doi.org/10.1007/s10147-020-01698-7

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  • DOI: https://doi.org/10.1007/s10147-020-01698-7

Keywords

  • Sorafenib
  • Adverse events
  • Dose adjustment
  • Prediction
  • Survival
  • Response