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.

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.

• Authors: 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
• Journal: Cancer (Cancer) Vol. 127 Issue 24 Pg. 4546-4556 (12 15 2021) ISSN: 1097-0142 [Electronic] United States
• PMID: 34726788 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2021 American Cancer Society.

Chemical References

• Bevacizumab
• Receptor, ErbB-2

Topics

• Bevacizumab (adverse effects)
• Clinical Trials, Phase III as Topic
• Humans
• Receptor, ErbB-2
• Triple Negative Breast Neoplasms (drug therapy)