In the phase III randomized ENESTnd trial, patients treated with nilotinib(Drug information on nilotinib) continued to show superior response after 18 months of follow-up. In addition, these patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia had reduced rates of progression on nilotinib vs imatinib(Drug information on imatinib).
Nilotinib (300 mg BID or 400 mg BID twice daily) achieved higher rates of major molecular response and complete cytogenetic response than imatinib (400 mg once daily). Significantly fewer patients on nilotinib progressed to accelerated phase or blast crisis, and there were fewer CML-related deaths on nilotinib.
"Molecular responses continue to deepen over time, and there continue to be fewer progression events and fewer deaths with nilotinib," said ENESTnd lead investigator Richard A. Larson, MD, a professor of medicine and director of the hematologic malignancies program at the University of Chicago. "Longer follow-up supports nilotinib as a new standard of care in patients with newly diagnosed CML."
The ENESTnd trial (Evaluating Nilotinib Efficacy and Safety in Clinical Trials of Newly Diagnosed Ph+CML Patients) enrolled 846 patients at 217 sites in 35 countries; planned follow-up is for five years. At a median follow-up of 18 months, at least 75% of the patients remained in the trial (ASCO 2010 abstract 6501; New Engl J Med 362: 2251-2259, 2010).
Out of 525 evaluable patients at 18 months, significantly more patients on nilotinib (69% at 300 mg and 63% at 400 mg) had a major molecular response than did patients on imatinib 400 mg (36%). Of the 442 patients who had a cytogenetic assessment, 99% on both doses of nilotinib experienced a complete cytogenetic response (CCyR) compared with 89% on imatinib.
Two patients on the nilotinib 300 mg dose and one on the 400 mg dose experienced disease progression vs 12 patients who received imatinib. There were also fewer CML-related deaths with nilotinib (two on the 300 mg dose and one on the 400 mg dose) than with imatinib (eight).
The ENESTnd investigators showed that rates of major molecular response for nilotinib (44% at 300 mg and 43% at 400 mg) were twice the rate for imatinib (22%) after one year. Rates of CCyR at 12 months were also significantly greater for nilotinib (80% at 300 mg and 78% at 400 mg) than for imatinib (65%).