Nilotinib versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia

Abstract

Nilotinib at a dose of either 300 mg or 400 mg twice daily was superior to imatinib in patients with newly diagnosed chronic-phase Philadelphia chromosome-positive CML. (ClinicalTrials.gov number, NCT00471497.

Nilotinib dose‐optimization in newly diagnosed chronic myeloid leukaemia in chronic phase: final results from ENESTxtnd

“…Notably, the median age and median time since diagnosis were generally comparable among patients in ENESTnd and ENESTxtnd (Saglio et al , 2010); however, the Sokal risk score distribution among patients in each study cannot be compared because Sokal risk scores were not collected in ENESTxtnd, and it is possible that the patient population in ENESTxtnd was healthier overall.…”

“…Whereas the protocol for ENESTxtnd allowed patients with insufficient response and those with drug‐related AEs to have their nilotinib dose actively escalated or reduced and re‐escalated, and then continue therapy, the ENESTnd protocol did not allow for nilotinib dose escalation and included more stringent guidelines for nilotinib dose reduction and re‐escalation than those in ENESTxtnd (Saglio et al , 2010). For example, following the second occurrence of a drug‐related, non‐haematological grade 2 AE (or first occurrence if grade 3/4) in the nilotinib 300‐mg twice‐daily arm of ENESTnd, the study protocol called for dose reduction to 400 mg once daily, and subsequent re‐escalation was allowed only if the AE resolved to grade ≤1 for 1 month (Saglio et al , 2010). The favourable outcomes (e.g., >50% MMR rate by 24 months) in patients with dose modifications in ENESTxtnd suggest that nilotinib dose optimization may be an appropriate strategy for the management of many nilotinib‐treated patients.…”

“…In the pivotal trial of frontline nilotinib versus imatinib in patients with CML‐CP (Evaluating Nilotinib Efficacy and Safety in Clinical Trials – Newly Diagnosed Patients [ENESTnd]), the efficacy and safety of nilotinib 300 mg twice daily and nilotinib 400 mg twice daily were compared with that of imatinib 400 mg once daily (Saglio et al , 2010). Throughout 6 years of follow‐up in ENESTnd, both nilotinib doses resulted in improved efficacy versus imatinib, including faster and higher rates of molecular responses and lower rates of disease progression and death due to advanced CML (Saglio et al , 2010; Kantarjian et al , 2011; Larson et al , 2012; Hughes et al , 2014a, 2015; Hochhaus et al , 2016a).…”

“…Throughout 6 years of follow‐up in ENESTnd, both nilotinib doses resulted in improved efficacy versus imatinib, including faster and higher rates of molecular responses and lower rates of disease progression and death due to advanced CML (Saglio et al , 2010; Kantarjian et al , 2011; Larson et al , 2012; Hughes et al , 2014a, 2015; Hochhaus et al , 2016a). By 6 years, 77·3% (nominal P  <   0·0001 versus imatinib), 79·0% (nominal P  <   0·0001 versus imatinib) and 61·1% of patients in the nilotinib 300‐mg twice‐daily, nilotinib 400‐mg twice‐daily and imatinib arms, respectively, achieved a major molecular response [MMR; defined as BCR‐ABL1  ≤   0·1% on the International Scale ( BCR‐ABL1 IS )]; among all randomized patients in each arm, 11 of 282 (nilotinib 300 mg twice daily; nominal P  =   0·0661 versus imatinib), 6 of 281 (nilotinib 400 mg twice daily; nominal P  =   0·0030 versus imatinib), and 21 of 283 patients (imatinib) progressed to accelerated phase/blast crisis (AP/BC) by 6 years (including after discontinuation of study treatment) (Hughes et al , 2015).…”

“…Estimated rates of overall survival at 6 years were 91·6% in the nilotinib 300‐mg twice‐daily arm (nominal P  =   0·7085 versus imatinib), 95·8% in the nilotinib 400‐mg twice‐daily arm (nominal P  =   0·0314 versus imatinib) and 91·4% in the imatinib arm (Hughes et al , 2015). The safety profile of nilotinib is well established and distinct from that of imatinib (Saglio et al , 2010; Kantarjian et al , 2011; Larson et al , 2012; Hughes et al , 2015; Hochhaus et al , 2016a). …”