Tolerability of bevacizumab and chemotherapy in a phase 3 clinical trial with human epidermal growth factor receptor 2–negative breast cancer: A trajectory analysis of adverse events

Edward H. Ip*, Santiago Saldana, Kathy D. Miller, Ruth C. Carlos, Ilana F. Gareen, Joseph A. Sparano, Noah Graham, Fengmin Zhao, Ju Whei Lee, Nathaniel S. O’Connell, David Cella, John D. Peipert, Robert J. Gray, Lynne I. Wagner

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: E5103 was a study designed to evaluate the efficacy and safety of bevacizumab. It was a negative trial for the end points of invasive disease–free survival and overall survival. The current work examines the tolerability of bevacizumab and other medication exposures with respect to clinical outcomes and patient-reported outcomes (PROs). Methods: Adverse events (AEs) collected from the Common Terminology Criteria for Adverse Events were summarized to form an AE profile at each treatment cycle. All-grade and high-grade events were separately analyzed. The change in the AE profile over the treatment cycle was delineated as distinct AE trajectory clusters. AE-related and any-reason early treatment discontinuations were treated as clinical outcome measures. PROs were measured with the Functional Assessment of Cancer Therapy–Breast + Lymphedema. The relationships between the AE trajectory and early treatment discontinuation as well as PROs were analyzed. Results: More than half of all AEs (57.5%) were low-grade. A cluster of patients with broad and mixed AE (all-grade) trajectory grades was significantly associated with any-reason early treatment discontinuation (odds ratio [OR], 2.87; P =.01) as well as AE-related discontinuation (OR, 4.14; P =.001). This cluster had the highest count of all-grade AEs per cycle in comparison with other clusters. Another cluster of patients with primary neuropathic AEs in their trajectories had poorer physical well-being in comparison with a trajectory of no or few AEs (P <.01). A high-grade AE trajectory did not predict discontinuations. Conclusions: A sustained and cumulative burden of across-the-board toxicities, which were not necessarily all recognized as high-grade AEs, contributed to early treatment discontinuation. Patients with neuropathic all-grade AEs may require additional attention for preventing deterioration in their physical well-being.

Original languageEnglish (US)
Pages (from-to)4546-4556
Number of pages11
JournalCancer
Volume127
Issue number24
DOIs
StatePublished - Dec 15 2021

Keywords

  • adverse events
  • breast cancer
  • drug treatment
  • early treatment discontinuation
  • patient-reported outcome
  • peripheral neuropathy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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