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Impact of age and comorbidity on safety outcomes in phase 1 trial participants for metastatic solid malignancies

Title: Impact of age and comorbidity on safety outcomes in phase 1 trial participants for metastatic solid malignancies
Authors: Shahnam, A; Hitchen, N; Manoharan, S; John, T; Mileshkin, L; Solomon, B; Sandhu, S; Luen, SJ; Desai, J; Tran, B
Publisher Information: Elsevier BV
Publication Year: 2025
Collection: The University of Melbourne: Digital Repository
Description: INTRODUCTION: The number of phase 1 clinical trials has been increasing globally over the past decade. However, patient recruitment remains skewed towards younger populations with older adults remaining underrepresented, limiting generalizability. Few studies have systematically examined the role of comorbidities as a determinant of safety outcomes in phase 1 trials. Thus, we aimed to investigate the impact of age and comorbidity on safety outcomes of phase 1 trial participants. MATERIALS AND METHODS: This retrospective analysis examined electronic health records of patients aged ≥18 years enrolled in phase 1 trials for metastatic solid malignancies between January 2020 and May 2023. Patients were stratified into two age groups (12. Eastern Cooperative Oncology Group (ECOG) performance status was also evaluated. Logistic regression models assessed associations between age, comorbidity, and safety outcomes: serious adverse events (SAE), dose-limiting toxicities (DLT), dose reductions/interruptions (DR/DI), cessation of treatment due to toxicity (COTT), and grade 3-5 toxicities. RESULTS: We included 229 patients, of whom 51 (22%) were aged ≥70 years. Among them, 79 (34%) experienced an SAE, 109 (48%) had DR/DI, 34 (15%) had COTT, 17 (7%) had DLT, and 99 (43%) developed grade 3-5 adverse events. Age was not significantly associated with a higher likelihood of adverse safety outcomes. However, patients with ECI ≥4 had significantly higher likelihood of SAE than those with ECI
Document Type: article in journal/newspaper
Language: English
ISSN: 1879-4068
Relation: https://hdl.handle.net/11343/363110
Availability: https://hdl.handle.net/11343/363110
Rights: https://creativecommons.org/licenses/by/4.0 ; CC BY
Accession Number: edsbas.2010D5D4
Database: BASE