Short-Term Cost Per Responder among New Tyrosine Kinase Inhibitors for Imatinib-Resistant CML in Chronic Phase (CML-CP) — Canada and Germany Perspectives.
Authors: Carpiuc Kim , Ouagari Khalid El , Stephens Jennifer , Botteman Marc , Feng WeiWei , Woodman Richard C. 
Published: October 2019

Abstract
BACKGROUND: For indications such as imatinib-resistant CML where data on durability of response or survival is still emerging, an alternative to modeling long-term cost-effectiveness is to perform a short-term analysis estimating average cost per responder based on cytogenetic responses, as the first 6–12 months have been shown to be a useful surrogate marker for treatment efficacy. This study incorporates cytogenetic response (MCyR or CCyR) with drug and adverse event (AE) costs to compare the 6-month cost per responder between dasatinib and nilotinib in patients with CML-CP.
METHODS: The average cost per responder was estimated by dividing the 6-month cost of treatment with cytogenetic response. Total cost of treatment included drug costs only for the primary analysis, but adding the cost of managing grade 3/4 AEs in sensitivity analyses. Based on time to event information, AEs were assumed to occur within the first 6 months of treatment. As no head-to-head comparison studies for nilotinib and dasatinib exist, data were obtained from studies believed to have the most comparable patient populations and similar length of study follow-up. Data on dasatinib were obtained from the published dasatinib phase II START-C study and the dasatinib FDA Oncologic Drug Advisory Committee (ODAC) briefing document. Two alternative cost perspectives were taken representing two cost structures. Dasatinib daily drug cost (140 mg/day) was assumed at Can$150.94 and Germany €146.66. For nilotinib, data were obtained from the nilotinib phase II 120-day efficacy and safety update clinical study reports submitted for registration, with daily drug (800 mg/day) cost based upon price parity with 800 mg/day imatinib. The model was developed from a payer perspective considering direct medical costs only.
RESULTS: Short-term (6-month) MCyR and CCyR rates for imatinib-resistant patients treated with 140 mg daily dasatinib were reported to be 31% and 22%. The corresponding numbers for 800 mg daily nilotinib were 51% and 31%, respectively. Primary cost drivers for AEs were myelosuppression events. Excluding the cost of AEs, the 6-month cost per MCyR was estimated to be Can$87,641 for dasatinib and Can$72,226 for nilotinib (Germany: €85,157 for dasatinib, €59,259 for nilotinib). The 6-month cost per CCyR was Can$123,480 for dasatinib, and Can$118,823 for nilotinib (Germany: €119,995 for dasatinib, €97,490 for nilotinib). Costs of treatment-related AEs for dasatinib and nilotinib were estimated at Can$10,429 and Can$4,861, respectively. Including AE costs in sensitivity analyses increased the cost per responder by 39% for dasatinib (7–17% for Germany) and by 13% for nilotinib (6–7% for Germany).
CONCLUSION: The average 6-month cost per MCyR and CCyR is lower for nilotinib compared to dasatinib when daily drug costs for nilotinib are assumed at price parity with imatinib 800mg regardless of whether AEs are included. The analysis incorporating AEs may be conservative considering only severe grade 3/4 AEs were included and indirect costs were not addressed. In the absence of head-to-head studies, these analyses should be updated as longer follow-up data become available, with ideal analyses using total costs and cytogenetic response rates at 1 year of follow-up, as well as expansion into long-term cost effectiveness analyses.