Incidence of grade 3/4 adverse events in imatinib resistant/intolerant chronic phase CML (CP-CML): A comparison of nilotinib and dasatinib

Abstract

17501 Background: Toxicities of new treatments may increase the care and resources required to manage patients (pts). The objective of this study was to compare the rates of Grade 3/4 AEs reported for nilotinib and dasatinib, the second generation tyrosine kinase inhibitors (TKIs) in imatinib resistant/intolerant CP-CML pts in preparation for an economic analysis. Methods: A systematic literature review was conducted to identify published articles, registration documents, or abstracts of clinical trials in CP-CML for nilotinib 400 mg bid and dasatinib 70 mg bid. The base case incidence rates were selected from the most rigorous sources, specifically data from the dasatinib product label and the nilotinib phase II trial, both populations having a median drug exposure of slightly >5 months. The AEs selected for the comparison were based on frequency (>5%) and/or high likelihood of incurring incremental costs for medical treatment/monitoring. The full ranges for the incidence of AEs (if available) were summarized from other papers/abstracts for sensitivity analyses in future economic analyses. Results: The Grade 3/4 hematologic AEs were the most common AEs (table below) and were ∼2 times higher for dasatinib than for nilotinib. Common Grade 3/4 biochemistry abnormalities included lipase elevations in 5% of nilotinib pts (1 pt developed a Grade 1/2 pancreatitis; no Grade 3/4 pancreatitis) and hypophosphatemia in 11% of dasatinib pts. Rates of Grade 3/4 non-hematologic AEs such as pleural effusion, GI bleeding, arrhythmia, and pneumonia/infection were >2–7 times higher for dasatinib than nilotinib, though they occurred in <5% of the population. Conclusions: The toxicity profiles of the second generation TKIs for imatinib resistant/intolerant CP-CML appear to be different and favor nilotinib with its reduced rates of Grade 3/4 AEs. Further analysis is required to understand the cost impact to health care payers of the differences in safety profiles among the new TKIs. [Table: see text] No significant financial relationships to disclose.