ENESTnd Trial: A Phase III Study Comparing Nilotinib with Imatinib as Front-Line Therapy of Early Chronic-Phase Chronic Myeloid Leukemia

Abstract

SUMMARY: The ENESTnd trial is a Phase III, randomized, open-label, multicenter trial, in which 846 patients with newly diagnosed chromosome Philadelphia-positive chronic-phase chronic myeloid leukemia were randomly assigned in a 1:1:1 ratio between three arms of treatment: imatinib mesylate 400 mg once daily, nilotinib 300 mg twice daily (b.i.d.), nilotinib 400 mg b.i.d. Nilotinib appeared superior to imatinib in terms of complete cytogenetic response at 12 months (77 vs 87 vs 85%; p < 0.001); major molecular response at 12 months (primary end point; BCR–ABL1 on an International Scale < 0.1%: 22 vs 44 vs 43%; p < 0.001); deep response at 4 years (BCR–ABL1IS< 0.0032%: 23 vs 40 vs 37%; p < 0.0001). Less progression to advanced phases at 4 years (0.7 vs 1.1 vs 4.2% on core treatment) converted into a slight advantage in terms of overall survival at 4 years for the nilotinib 400 mg b.i.d. arm in Sokal intermediate- and high-risk patients. Tolerance and quality of life were in favor of nilotinib, with the noteworthy exception of cardiovascular events (1.5 vs 6.4vs 8.7% at 4 years). This trial led to the approval of nilotinib 300 mg b.i.d. as front-line therapy of chronic-phase chronic myeloid leukemia in 2010.