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

Abstract

Practice Points• Nilotinib is a potent inhibitor of the BCR-ABL1 kinase involved in the pathogenesis of chronic myeloid leukemia (CML), and displays activity on some imatinib-resistant mutants of the kinase.• Nilotinib is one of the second-generation tyrosine-kinase inhibitors that challenge the role of imatinib, the first-generation one, in the treatment of CML.• The ENESTnd trial is a three-arm Phase III study comparing imatinib 400 mg/day versus nilotinib 300 mg/12 h versus nilotinib 400 mg/12 h in 846 newly diagnosed patients with chronic-phase CML, with the main end point of major molecular response (reduction of 3 logs of the BCR-ABL1 transcript) at 12 months of therapy.• Results of the trial have been published after 1-year of follow-up, and updated at 2, 3 and 4 years.• Nilotinib yields more frequent, deeper and faster responses, both cytogenetic and molecular, across all riskgroups of the disease, as compared with imatinib.• Nilotinib leads to a lower rate of progression towards advanced phases of the disease, leading to a slight significant gain in overall survival over imatinib.• Nilotinib has a better tolerance than imatinib with regards to symptoms interfering with daily life, but has a more important hepato-pancreatic, metabolic and cardiovascular toxicity, justifying to closely select and monitor patients who might be candidates for the drug.• Nilotinib has been approved by the US FDA and European health authorities as front-line therapy of chronicphase CML on the basis of these results.• Nilotinib, alone or combined to other drugs, such as interferon, is currently part of trials aiming at a more radical control of the disease and at long-term treatment discontinuation in a significant subset of patients.For reprint orders, please contact: reprints@futuremedicine.com Int.