title: Treatment patterns, overall survival, healthcare resource use and costs in elderly Medicare beneficiaries with chronic myeloid leukemia using second-generation tyrosine kinase inhibitors as second-line therapy.
abstract: Objective Though the median age at diagnosis is 64 years, few studies focus on elderly (≥65 years) patients with chronic myeloid leukemia (CML). This study examines healthcare outcomes among elderly Medicare beneficiaries with CML who started nilotinib or dasatinib after imatinib. Research design and methods Patients were identified in the Medicare Research Identifiable Files (2006-2012) and had continuous Medicare Parts A, B, and D coverage. Main outcome measures Treatment patterns, overall survival (OS), monthly healthcare resource utilization and medical costs were measured from the second-line tyrosine kinase inhibitor (TKI) initiation (index date) to end of Medicare coverage. Results Despite similar adherence, dasatinib patients (N = 379) were more likely to start on the recommended dose (74% vs. 53%; p < 0.001), and to have dose reductions (21% vs. 11%, adjusted hazard ratio [HR] = 1.94; p = 0.002) or dose increases (9% vs. 7%; adjusted HR = 1.81; p = 0.048) than nilotinib patients (N = 280). Fewer nilotinib patients discontinued (59% vs. 67%; adjusted HR = 0.80; p = 0.026) or switched to another TKI (21% vs. 29%; adjusted HR = 0.72; p = 0.044) than dasatinib patients. Nilotinib patients had longer median OS (>4.9 years vs. 4.0 years; p = 0.032) and 37% lower mortality risk than dasatinib patients (adjusted HR = 0.63; p = 0.008). Nilotinib patients had 23% fewer inpatient admissions, 30% fewer emergency room visits, 13% fewer outpatient visits (all p < 0.05), and lower monthly medical costs (by $513, p = 0.024) than dasatinib patients. Limitations Lack of clinical assessment (disease phase and response to first-line therapy) and retrospective nature of study (unobservable potential confounding factors, non-randomized treatment choice). Conclusions In the current study of elderly CML patients, initiation of second-line TKIs frequently occurs at doses lower than the recommended starting doses and, despite this, many patients require dose adjustments. Here, nilotinib patients required fewer dose adjustments than dasatinib patients. Further research focusing on elderly CML patients is warranted in order to help define future best clinical practices.
authors.affiliation: a Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins , Baltimore , MD , USA ;
authors.forename: B Douglas
authors.initials: BD
authors.lastname: Smith
authors.affiliation: b Harvard University , Cambridge , MA , USA ;
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: c Analysis Group Inc. , Montreal, Quebec, Canada ;
authors.forename: Dominick
authors.initials: D
authors.lastname: Latremouille-Viau
authors.affiliation: c Analysis Group Inc. , Montreal, Quebec, Canada ;
authors.forename: Annie
authors.initials: A
authors.lastname: Guerin
authors.affiliation: b Harvard University , Cambridge , MA , USA ;
authors.forename: Daniel
authors.initials: D
authors.lastname: Fernandez
authors.affiliation: d Novartis Pharmaceuticals Corporation , East Hanover , NJ , USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000069439:Dasatinib / Q000008:administration & dosage; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D006278:Medicare; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000008:administration & dosage; D012189:Retrospective Studies; D014481:United States
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; C498826:nilotinib; D000069439:Dasatinib
keywords: Chronic myeloid leukemia; Healthcare resource use; Medical costs; Medicare; Overall survival; Treatment patterns; Tyrosine kinase inhibitors