PS1181 DOSING PATTERNS OF DASATINIB AND NILOTINIB USE IN SIMPLICITY, AN OBSERVATIONAL STUDY IN CHRONIC‐PHASE CHRONIC MYELOID LEUKEMIA (CP‐CML) PATIENTS (PTS) IN ROUTINE CLINICAL PRACTICE
Authors: J. Cortes, C. Gambacorti‐Passerini, S. Goldberg, M. Mauro, C. Chen, C. Davis
Journal: HemaSphere (2019)

Background: Outside of clinical trials,dosing patterns of dasatinib (DAS) and nilotinib (NIL) in CP‐CML pts have not been well documented. SIMPLICITY (NCT01244750) is an ongoing observational study (since 2010) exploring tyrosine kinase inhibitor (TKI) use in routine clinical practice among CP‐CML pts in Europe and the United States (US). Aims: This analysis compares dosing patterns and explores predictors of dose reductions in first‐line (1L) pts starting on DAS (100 mg once daily [QD]) vs NIL (300 mg or 400 mg twice daily [BID]). Methods: SIMPLICITY pts receiving 1L DAS QD (n = 405/417) and 1L NIL BID (n = 350/408)were includedin this analysis. Twelve DAS and 58 NIL pts were excluded as they received treatment at different dosing frequencies. Baseline (BL) characteristics, demographics, and dosing patterns were analyzed descriptively. Statistical comparisons were made using t‐tests and the Mann–Whitney U test for continuous variables; chi‐square tests were used for categorical variables. Multivariate logistic regression models were used to identify factors associated with dose reductions. TKI class (DAS vs NIL), starting dose, gender, region, practice type, and BL comorbidities were adjusted in the multivariate model. Results: In this non‐controlled study, 92.1% (n = 373) of DAS pts started on 100 mg QD compared with 70.1% (n = 247) and 13.6% (n = 34) of NIL pts starting on 300 mg (1L approved dose) and 400 mg BID (approved in second‐line and above [≥2L]), respectively. All BL characteristics were broadly similar across the dosing groups. The proportions of pts receiving either dose increases or reductions were similar across the dosing groups. However, mediantime to dose reduction was significantly shorter in pts receiving 300 mg NIL BID (median 84.0 days; interquartile range, [IQR] 29, 226]) than those receiving 100 mg DAS QD (median 139.5 days; IQR 44, 588.5; P = 0.0169), and was numerically shorter for pts receiving 400 mg NIL BID (median 80.5 days; IQR 29, 474). Intolerance was the main reason for dose reductions for 100 mg DAS QD (78.2%), and 300 mg (79.0%) or 400 mg NIL BID (78.6%). Factors associated with dose reduction were older age at TKI start, female gender, region (US), academic practice, and fatigue and musculoskeletal comorbidities at BL. Using logistic regression, age at TKI start, female gender, and academic practice were strong predictors for dose reductions ( P &lt; 0.05) and US region was a weak predictor (P = 0.0882). Starting dose was not a significant predictor. In pts receiving dose reductions, median duration of therapy (DoT) was significantly longer for those starting on DAS 100 mg QD vs those starting on NIL 400 mg BID (median [IQR]: 47.5 months [20.4, 60.4] vs26.2 months [17.9, 26.2]; P = 0.0469) and numerically longer for DAS 100 mg QD vs NIL 300 mg BID (median [IQR]: 36.4 months[13.2, 60.4])( Table ). Summary/Conclusion: The majority of 1L NIL pts started on 300 mg NIL BID; however, about one in ten pts started on 400 mg BID, the dose indicated for the ≥2L setting. While overall changing patterns of dose and reasons for dose reductions were similar across the three dosing groups, among the two standard 1L dose regimens, time to dose reduction was significantly shorter for NIL 300 mg BID than DAS 100 mg QD. Furthermore, in pts receiving dose reductions, DAS 100 mg QD was associated with longer DoT compared with NIL 400 mg BID, with tolerability likely playing a role. This, and theidentified predictors for dose reduction, provide information that could aid clinical decisions on dose optimization. image