The Lynx Group

Nilotinib Sustains 24-Month Superiority to Imatinib in CML

October 2011, Vol 2, No 6

The BCR-ABL inhibitor nilotinib (Tasigna) was developed as a selective treatment for patients with chronic myeloid leukemia (CML) who are not responding appropriately to imatinib (Gleevec) therapy. Previous results from the Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Patients (ENESTnd) study showed 12-month superior efficacy for nilotinib over imatinib in patients with newly diagnosed Philadelphia chromosome– positive (Ph+) CML in the chronic phase. New results for additional 12-month follow-up show that patients treated with nilotinib sustained their molecular response for 24 months (Kantarijian HM, et al. Lancet Oncol. 2011;12:841-851).

In this phase 3, multicenter, openlabel, randomized study, 847 adult patients with chronic-phase Ph+ CML were randomized to oral therapy with nilotinib 300 mg twice daily (N = 282), nilotinib 400 mg twice daily (N = 281), or imatinib 400 mg once daily (N = 283). The primary end point was major molecular response at 12 months.

At 24 months, a major molecular response occurred in 71% of patients receiving nilotinib 300 mg twice daily, in 67% of patients receiving nilotinib 400 mg twice daily, and in only 44% of patients receiving imatinib 400 mg once daily (P <.001 for both comparisons vs imatinib). In addition, a complete molecular response occurred significantly more often in the 2 nilotinib groups (26% and 21%, respectively) than in the imatinib group (10%).

Furthermore, BCR-ABL transcript levels were decreased below the threshold of 0.1% about 12 months earlier with nilotinib than with imatinib, and emerging BCR-ABL mutations in the nilotinib groups were 50% less than in the imatinib group.

Progression to accelerated or blastphase CML during treatment, including clonal evolution, occurred in 7 patients in the nilotinib groups and in 17 patients in the imatinib group. At 24 months, survival was comparable in all treatment groups, but CML-related death occurred less often with nilotinib (8 patients) than with imatinib (10 patients).

The only grade 3 or 4 adverse effects occurring more frequently with nilotinib were headache and rash. How - ever, in the second 12-month follow-up study, 8 additional serious adverse events occurred—7 in the nilotinib group and 1 in the imatinib group. The investigators believe that as a result of nilotinib’s faster, and more durable responses and significantly lower associated risk of progression, the drug should be considered a firstline therapy for CML in chronic phase.

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