{"doi":"10.1002/cncr.33992","title":"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.","journal":"Cancer","year":2021,"id":207883,"datarank":0.26599149058096244,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.02457580371584736,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.02457580371584736,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":2,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9552,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT00433511"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":482246,"name":"Santiago Saldana","orcid":null,"position":1,"is_corresponding":false},{"id":353356,"name":"Kathy D. Miller","orcid":"0000-0002-7125-883X","position":2,"is_corresponding":false},{"id":280774,"name":"Ruth C. Carlos","orcid":"0000-0001-7055-7662","position":3,"is_corresponding":false},{"id":562897,"name":"Ilana F. Gareen","orcid":"0000-0002-0457-5595","position":4,"is_corresponding":false},{"id":245492,"name":"Joseph A. Sparano","orcid":"0000-0002-9031-2010","position":5,"is_corresponding":false},{"id":793900,"name":"Noah Graham","orcid":"0009-0009-0622-683X","position":6,"is_corresponding":false},{"id":288837,"name":"Fengmin Zhao","orcid":"0000-0001-9826-3703","position":7,"is_corresponding":false},{"id":516734,"name":"Ju‐Whei Lee","orcid":"0000-0003-2068-8511","position":8,"is_corresponding":false},{"id":562898,"name":"Nathaniel S. O’Connell","orcid":"0000-0002-3827-5152","position":9,"is_corresponding":false},{"id":232516,"name":"David Cella","orcid":"0000-0002-9881-4541","position":10,"is_corresponding":false},{"id":445512,"name":"John Devin Peipert","orcid":"0000-0001-5762-7881","position":11,"is_corresponding":false},{"id":241715,"name":"Robert J. Gray","orcid":"0000-0002-5724-4917","position":12,"is_corresponding":false},{"id":5119,"name":"Lynne I. Wagner","orcid":"0000-0001-9685-4796","position":13,"is_corresponding":false},{"id":382805,"name":"Edward H. Ip","orcid":"0000-0002-4811-4205","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-18T23:51:53.662668Z","pmid":"34726788","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}