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.

Keywords:

• Chronic myeloid leukemia
• Healthcare resource use
• Medical costs
• Medicare
• Overall survival
• Treatment patterns
• Tyrosine kinase inhibitors

Declaration of funding

Funding for this research was provided by Novartis Pharmaceuticals Corporation.

 Author contributions: The study sponsor was involved in all stages of the study research and manuscript preparation. All authors participated in the design and analytical approach of the study and contributed to the manuscript development. Data were collected, cleaned, and analyzed by Harvard University. Results were summarized and interpreted in collaboration with all other authors. Manuscript drafts were prepared by the authors with editorial assistance from a professional medical writer ultimately paid by the sponsor. All the authors vouch for the accuracy and completeness of the data reported and the adherence of the study to the protocol, and all the authors made the decision to submit the manuscript for publication.

Declaration of financial/other relationships

L.C. has disclosed that she is an employee of Novartis Pharmaceuticals Corporation and owns stock/stock options. D.L.-V. and A.G. have disclosed that they are employees of Analysis Group Inc., which has received consultancy fees from Novartis Pharmaceuticals Corporation. B.D.S., J.L., and D.F. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

 CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

Medical writing assistance was provided by Ana Bozas PhD, an employee of Analysis Group Inc. Christopher H. Keir MD, medical director at Novartis Pharmaceuticals Corporation, Zhou Zhou MSc, an employee of Analysis Group Inc., and Shivani K. Mhatre, who was an employee of Novartis Pharmaceuticals Corporation at the time the study was conducted, provided assistance with the study design, interpretation of the results, and manuscript edit.

 Previous presentation: A synopsis of the current research was presented in poster format at the 56th American Society of Hematology Annual Meeting and Exposition, San Francisco, CA, USA, 6–9 December 2014.