ENESTnd: Nilotinib Superior to Imatinib for CML After 3 years

Three-year results from the ENESTnd trial show continued superiority of nilotinib over imatinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML) in chronic phase, according to a new paper published online ahead of print in Leukemia.

Microscopic analysis of blood smear stained with May-Grnwald/Giemsa, from a patient with CML; source: Dr Ramon Simon-Lopez, Wikimedia Commons

Both 1- and 2-year analyses of the Evaluating Nilotinib Efficacy and Safety in Clinical Trials Newly Diagnosed Patients phase III trial showed faster and higher rates of cytogenetic response, major molecular response, and lower rates of progression to accelerated or blast phase CML, along with fewer CML-related deaths. Researchers led by Richard A. Larson, MD, reported 3-year results in a total of 846 patients divided between a nilotinib 300 mg twice-daily group (282 patients), a nilotinib 400 mg twice-daily group (281 patients), and an imatinib 400 mg once daily group (283 patients).

At study cutoff in July 2011, about 95% of patients in each group were still on active follow-up or had died. In the nilotinib 300 mg group, 200 patients (70.9%) were still taking the study drug, and 207 patients (73.7%) in the nilotinib 400 mg group were still taking the study drug, compared with 175 patients (61.8%) in the imatinib group.

The major molecular response rate was 73% in the nilotinib 300 mg group and 70% in the nilotinib 400 mg group, both significantly better than the 53% in the imatinib group (P ≤ .0001 for both). Both nilotinib arms were also superior with regard to deeper molecular responses based on BCR-ABL levels.

Since the 2-year analysis there were no new cases where patients progressed to accelerated phase/blast crisis while on core treatment. Over the full course of the study, a total of 2 patients in the nilotinib 300 mg arm, 3 patients in the nilotinib 400 mg arm, and 12 patients in the imatinib arm progressed to accelerated phase/blast crisis. This resulted in a significantly lower risk of progression while on treatment for either dose of nilotinib vs. imatinib, with a hazard ratio of 0.16 for the 300 mg dose (P = .0059 vs. imatinib) and 0.25 for the 400 mg dose (P = .0185).

At 3 years, the overall survival rate for the nilotinib 300 mg group was 95.1%; the rate was 97.0% for the 400 mg patients and 94.0% for the imatinib group. When considering only those deaths attributed to CML, the rates were 98.1%, 98.5%, and 95.2%, respectively. This yielded a HR for survival of 0.35 for the 300 mg group (P = .0356 vs. imatinib) and 0.28 for the 400 mg group (P = .0159 vs. imatinib).

The authors wrote that the 3-year results are particularly important for CML research, as previous work has shown that most disease progression events occur within the first 3 years of treatment. “Results from ENESTnd demonstrate that, compared with imatinib, patients treated with nilotinib had lower rates of progression throughout this entire 3-year period,” they wrote.

Furthermore, the deeper molecular response with nilotinib is significant in the context of ongoing research into treatment cessation studies for CML patients in remission.

“There is a need to increase the number of patients with the deepest levels of response, and results from ENESTnd suggest that first-line nilotinib therapy may increase the number of patients eligible for treatment cessation,” Larson and colleagues noted. “Taken together, these data suggest that nilotinib is superior to imatinib for the treatment of patients with newly diagnosed Philadelphia chromosome-positive CML in chronic phase and should be preferred as the first-line therapeutic option for this population.”