DDMODEL00000302: Time_to_event_Peripheral_Neuropathy_2019

Short description:
Peripheral neuropathy (PN) is a common long-term debilitating toxicity of antimicrotubule agents. PN was the most frequent adverse event resulting in dose modifications and/or discontinuation of treatment for valine-citrulline-monomethylauristatin E antibody-drug conjugates (ADCs) developed at Genentech. A pooled time-to-event analysis across eight ADCs (~700 patients) was performed to evaluate the relationship between the ADC exposure and the risk for developing a clinically significant (grade ? 2) PN. In addition, the impact of demographic and pathophysiological risk factors on the risk for PN was explored. The time-to-event analysis suggested that the development of PN risk increased with ADC exposure, treatment duration, body weight, and previously reported PN. This model can be used to inform clinical strategies such as adaptations to dosing regimen and/or treatment duration as well as inform clinical eligibility to reduce the incidence of grade ? 2 PN.
Original code |
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Matts Kågedal
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Context of model development: | Variability sources in PK and PD (CYP, Renal, Biomarkers); Dose & Schedule Selection and Label Recommendation; |
Model compliance with original publication: | Yes; |
Model implementation requiring submitter’s additional knowledge: | No; |
Modelling context description: | A pooled time-to-event analysis across eight ADCs (~700 patients) was performed to evaluate the relationship between the ADC exposure and the risk for developing a clinically significant (grade â?¥ 2) PN. In addition, the impact of demographic and pathophysiological risk factors on the risk for PN was explored.; |
Modelling task in scope: | estimation; |
Nature of research: | Early clinical development (Phases I and II); |
Therapeutic/disease area: | Oncology; |
Annotations are correct. |
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This model is not certified. |