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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
Author(s) -
Ip Edward H.,
Saldana Santiago,
Miller Kathy D.,
Carlos Ruth C.,
Gareen Ilana F.,
Sparano Joseph A.,
Graham Noah,
Zhao Fengmin,
Lee JuWhei,
O’Connell Nathaniel S.,
Cella David,
Peipert John D.,
Gray Robert J.,
Wagner Lynne I.
Publication year - 2021
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.33992
Subject(s) - medicine , tolerability , common terminology criteria for adverse events , discontinuation , adverse effect , breast cancer , oncology , bevacizumab , hazard ratio , clinical trial , cancer , chemotherapy , confidence interval
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.