Dose-optimized nilotinib (Tasigna) increased the rates of major molecular response in patients with newly diagnosed chronic myeloid leukemia (CML) in the chronic phase (CP) in the Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Extending Molecular Responses (ENESTxtnd) study. According to the final results of this study presented at ASH 2015, the cumulative major molecular response rates were 70.8% by 12 months and 81.0% by 24 months in patients managed with the dose optimization strategy.
“The results from this study demonstrated the feasibility of nilotinib dose optimization with high response rates among patients with dose adjustments and a high rate of successful dose re-escalation among patients with dose reductions,” said Timothy P. Hughes, MD, MBBS, Cancer Theme Leader, South Australian Health and Medical Research Institute, Adelaide, Australia. “Overall, results from ENESTxtnd were consistent with those of prior studies and support frontline nilotinib for patients with newly diagnosed CML-CP.”
The use of frontline nilotinib in the Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients (ENESTnd) study achieved earlier and higher rates of molecular response in patients with CML-CP versus frontline imatinib (Gleevec).
ENESTxtnd was conducted to further investigate the efficacy and safety of frontline nilotinib and to evaluate new nilotinib dose-optimization strategies.
The ENESTxtnd study enrolled 421 newly diagnosed patients aged >18 years who had not received previous CML therapy and ECOG performance status of 0 to 2.
Patients received nilotinib 300 mg and dose optimization (escalation, reduction, and re-escalation) as recommended per the study protocol. Dose escalation to 400 mg was permitted for all patients with suboptimal response or treatment failure.
Of the 421 patients, 78% completed the 24-month protocol to remain on nilotinib, with only 22% of patients discontinuing treatment. Of those who completed 24 months of treatment, 76% remained at 300 mg, 20% escalated to 400 mg, and 4% of patients escalated to 450 mg.
Of the 144 patients whose dose was reduced, 106 attempted dose re-escalation, which was successful in 92 patients.
“We are cautious in interpreting the data,” said Dr Hughes, “but cumulative rates of major molecular response look extremely good compared to ENESTnd.”
By 12 months, approximately 71% of patients had achieved a major molecular response in ENESTxtnd compared with 55% of patients in ENESTnd; by 24 months, 81% of patients in the ENESTxtnd study had achieved major molecular response compared with 71% of patients in the ENESTnd trial.
The safety profile of nilotinib in the ENESTxtnd study was similar to other reports of frontline nilotinib.