Lower Healthcare Resource Utilization Associated with Managing Nilotinib Related Adverse Events in Chronic Myeloid Leukemia (CML) Patients – Evidence From a Clinical Practice Setting Study.

Only few studies have characterized the healthcare burden associated with managing adverse events (AEs) in the second-line treatment of CML. Information on incidence of AEs and resource utilization in managing these events would be valuable treatment related attributes. Nilotinib is a potent and selective BCR-ABL kinase inhibitor that is approved for the treatment of Ph+ CML patients in Chronic Phase (CP) and Accelerated Phase (AP), who were intolerant or have failed previous imatinib treatment. Dasatinib is another approved second-line agent in the treatment of imatinib resistant or intolerant CML. Nilotinib and dasatinib have shown differences in their safety profiles in clinical trials.

This study compared the safety profile of nilotinib, observed in a large study of CML patients in a clinical practice setting from participating North American sites to product information of nilotinib and dasatinib, and also compare potential cost differences between the two settings.

Adult patients with imatinib resistant or intolerant Ph+ CML in CP, AP, and blast crisis (BC) were recruited to participate in this phase IIIb, open label, multi-center ENACT (Expanding Nilotinib Access in Clinical Trials) study. Data obtained from the participating North America sites is presented here. Patients who previously failed dasatinib treatment were also allowed to participate. The primary objective of the ENACT study was to obtain additional safety information with nilotinib treatment in a clinical practice setting. Patients received nilotinib 400 mg twice daily (BID). Patients were not permitted to dose escalate. A comprehensive set of hematological and non-hematological adverse event information was obtained in the study. Follow-up treatment in managing the AE, either as dose reduction, dose interruption, or other treatment is also recorded. Incidence of adverse events reported in this study was compared to nilotinib and dasatinib product information. Healthcare resource utilization was estimated from a US health plan perspective by constructing six-month marginal cost increase in patients who received follow-up care for the management of adverse event. Cost data were obtained from MedStat market scan database that contained over 5,000 CML patients. Multivariate regression models and sensitivity analyses were conducted to derive the marginal cost estimates.

A total of 207 patients (172 CP pts, 15 AP pts, and 20 BC pts) were enrolled in the study from several sites in North America between Jan 2006 – Oct 2008. The median age was 54 years. At study completion, 48% were continuing on study treatment, 25% discontinued treatment due to unsatisfactory therapeutic effect, 14% discontinued due to AEs, and 13% discontinued due to other reasons. Percentage of patients with grade 3/4 hematological AEs suspected of being study drug related in CP, AP were: thrombocytopenia (12%, 20%), neutropenia (9%, 27%) and anemia (1.2%, 13%). The most frequent non hematologic AEs (all grades) included rash, headache, nausea, and fatigue. Study patients requiring additional therapy for the reported hematological adverse events was less than 50% in most cases. Dose reductions and dose interruptions of greater than 5 days to manage AEs occurred in 2.3% and 32% patients, respectively, with median duration of dose interruption of 12 days in CP patients and 7 days in AP patients. Total medical costs associated with managing the adverse events, estimated from MedStat cost data, for both hematological and non-hematological AEs observed in this analysis based on patients receiving additional treatment were $6,314 for CML patients in CP and AP, over a six-month treatment period. Medical costs associated with managing hematological adverse events made up the majority of these costs. The estimated costs from this study were significantly lower compared to the estimated burden of the AEs in the product information for nilotinib or dasatinib ($9,730 and $12,372, respectively).

Nilotinib related adverse event costs observed in this large clinical practice setting study compare favorably to the estimated costs from product information from nilotinib and dasatinib. The analysis is comprehensive in estimating the healthcare costs by characterizing the incidence of the AEs, and managing of the AEs through dose reductions, dose interruption or follow-up care.

Guerin:Novartis: Consultancy, I am working for Analysis Group Inc and Analysis Group Inc received funds from Novartis to conduct the analysis. Bollu:Novartis Oncology: Employment. Williams:Novartis Pharmaceuticals: Employment.