Decision modelling using time on treatment data: evaluating the survival benefit of nilotinib versus imatinib in patients with chronic phase Ph+ CML

BACKGROUND: The ENESTnd randomised controlled trial demonstrated that nilotinib in newly diagnosed Philadelphia chromosome positive (Ph+) chronic phase chronic myeloid leukaemia (CML) has clinical superiority in terms of molecular and cytogenetic response over imatinib. However the exact relationship between improvements in major molecular response (MMR), complete cytogenetic response (CCyR) and improvements in long-term survival is as yet unknown. OBJECTIVES: (1) to evaluate the survival benefit of first-line nilotinib compared to first-line imatinib for the treatment of Ph+ chronic phase CML, and (2) to develop a decision analytic model which avoids the uncertainty of using surrogate response outcomes in economic evaluations. METHODS: A decision analytic model of first-line nilotinib compared to first-line imatinib was constructed for newly diagnosed chronic phase Ph+ CML patients. Time on treatment data from the ENESTnd trial was used to model the effectiveness of nilotinib and imatinib. This approach allows the explicit modelling of all treatment failures (patients who fail to achieve or lose response, experience intolerable adverse events or those who discontinue treatment) and provides a measure of those that continue to benefit from treatment. RESULTS: The mean undiscounted survival was estimated to be 11.80 years in the nilotinib arm compared to 10.44 years in the imatinib arm; a difference of 1.36 life-years (LYs). Using a discounting rate of 3.5%, patients will accrue an additional 0.88 LYs in the nilotinib arm compared to the imatinib arm. CONCLUSIONS: The results suggest that nilotinib produces substantially greater long-term survival than treatment with imatinib. The use of time on treatment data avoids the need for surrogate response outcomes and their associated uncertainty.