Assessment of Anticholinergic Burden scales and Measures for Estimating Anticholinergic Exposure in Retrospective u.s. Database Analyses

Abstract

s211 status (RECIST 1.1 responder/non-responder) at a 6-month landmark, we performed Kaplan-Meier analysis of subsequent OS and sensitivity analyses. Time-dependent Cox regressions were also performed. Results: Overall response rate was 19% (56/292) for nivolumab and 12% (36/290) for docetaxel. The number of responders (non-responders) at 6 months was 49 and 26 (132 and 149) among nivolumab and docetaxel patients, respectively. For nivolumab, median post-landmark OS was 12.2 months (95% CI: 9.5-15.1) for non-responders and not reached (NR) (95% CI: 23.9-NR) for responders. For docetaxel, median post-landmark OS was 7.1 months (95% CI: 5.4-9.4) for non-responders and 13.8 months (95% CI: 11.1-28.7) for responders. The hazard ratio between responders and non-responders was 0.24 (95% CI: 0.15-0.39) in the nivolumab arm and 0.55 (95% CI: 0.34-0.88) in the docetaxel arm. Time-dependent Cox analyses showed significantly reduced responders' mortality, and the risk reduction was significantly greater for nivolumab than for docetaxel (p= 0.003). Sensitivity analysis using alternative landmarks yielded qualitatively similar findings. ConClusions: In CheckMate 057, response at 6-months was significantly and positively associated with subsequent survival in both arms; however, the relationship was stronger for nivolumab than for docetaxel. Additionally, non-responders to nivolumab showed a longer median post-landmark survival than non-responders to docetaxel. These findings support incorporating separate response-based survival curves by treatment arm in economic models, especially when comparing an I-O to a non-I-O treatment.

An Evaluation of Longitudinal Measures of Anticholinergic Exposure for Application in Retrospective Administrative Data Analyses

“…However, as both anticholinergic dose and theoretical potency have individually been identified as contributors to anticholinergic burden, a measure that considers both could potentially capture the impact of the interaction between patient-specific dosing and presumed anticholinergic activity. To try to fill this gap, the Cumulative Anticholinergic Burden (CAB) measure was developed, which considers both dosing intensity and anticholinergic potency [based upon the Anticholinergic Cognitive Burden (ACB) scale] in its calculation [19]. Such a measure may provide a more robust method to capture cumulative anticholinergic exposure.…”