Modernizing the assessment and reporting of adverse events in oncology clinical trials using complementary statistical approaches: a case study of the MOTIVATE trial.

Autor: Morisseau M; Biostatistics & Health Data Science Unit, Oncopole Claudius Regaud- IUCT-O, 1 Avenue Irène Joliot-Curie, Toulouse, Cedex 9, 31059, France., Gomez-Roca C; Department of Medical Oncology, Oncopole Claudius Regaud- IUCT-O, Toulouse, France., Viala M; Department of Medical Oncology, Institut du Cancer de Montpellier (ICM), Montpellier, France., Rabeau A; Department of Pneumology, CHU Toulouse Larrey, Toulouse, France., Loirat D; Department of Medical Oncology, Institut Curie, Paris, Saint-Cloud, France.; Department of Drug Development and Innovation (D3i), Institut Curie, Paris, Saint-Cloud, France., Munsch N; Department of Medical Oncology, CH Albi, Albi, France., Thomas K; Department of Medical Oncology, Oncopole Claudius Regaud- IUCT-O, Toulouse, France., Pages C; Department of Dermatology Oncology, Oncopole Claudius Regaud- IUCT-O, Toulouse, France., Korakis I; Department of Medical Oncology, Oncopole Claudius Regaud- IUCT-O, Toulouse, France., Sibaud V; Department of Dermatology Oncology, Oncopole Claudius Regaud- IUCT-O, Toulouse, France., Delord JP; Department of Medical Oncology, Oncopole Claudius Regaud- IUCT-O, Toulouse, France., Filleron T; Biostatistics & Health Data Science Unit, Oncopole Claudius Regaud- IUCT-O, 1 Avenue Irène Joliot-Curie, Toulouse, Cedex 9, 31059, France. filleron.thomas@iuct-oncopole.fr.; Université Paris-Saclay, CESP, INSERM U1018 Oncostat, labeled Ligue Contre le Cancer, Villejuif, France. filleron.thomas@iuct-oncopole.fr., Cabarrou B; Biostatistics & Health Data Science Unit, Oncopole Claudius Regaud- IUCT-O, 1 Avenue Irène Joliot-Curie, Toulouse, Cedex 9, 31059, France.
Jazyk: angličtina
Zdroj: Investigational new drugs [Invest New Drugs] 2024 Nov 04. Date of Electronic Publication: 2024 Nov 04.
DOI: 10.1007/s10637-024-01481-9
Abstrakt: The reporting of adverse events (AEs) is fundamental to characterize safety profiles of novel therapeutic drug classes, however, conventional analysis strategies are suboptimal tools for this task. We therefore attempted to contribute to the modernization of AE analysis by encompassing the dimension of time, the duration and the recurrent nature of AEs induced by these extended treatment durations. This paper presents and highlights the benefits of alternative approaches to modernize AE analysis based on the MOTIVATE prospective study modeling immune-related AEs (irAEs) in patients with solid tumors (regardless of the primary site) treated with immune checkpoint inhibitor irrespective of disease stage. The probability of presenting an irAE over time was estimated using the prevalence function. The time-to-onset (TTO) and the mean number of recurrent irAEs were also assessed. Among the 147 patients analyzed, 39.7% had a melanoma, 37.7% a non-small cell lung cancer (NSCLC) and 74.8% were treated for metastatic disease. Despite a higher proportion of melanoma patients presenting at least one irAE, the prevalence of irAEs was lower in melanoma than in NSCLC patients over time. TTO analysis showed that irAEs occurred earlier in NSCLC patients whereas melanoma patients experienced more recurrent irAEs over the long-term. The prevalence function of non-metastatic and metastatic patients revealed different long-term toxicity profiles. These alternative methodologies capture different toxicity patterns (time-to-onset, recurrent, acute episodic or long-term moderate AEs) and provide a more consistent safety assessment for new therapeutics, thereby assisting clinicians and health authorities in their therapeutic decision-making processes.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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