Results from the Phase 3, international, randomised ENESTnd trial have demonstrated the superior efficacy of nilotinib over imatinib with significantly higher rates of major molecular response (MMR), complete cytogenetic response (CCyR) and significantly lower rates of progression to AP/BC on treatment.

A further follow-up of around 18 months in 846 CML-CP patients has continued to show superiority of nilotinib over imatinib. The overall best MMR rate was 66%and 62% for nilotinib 300 mg and 400 mg bid (p<0.0001), respectively, versus imatinib (40%). The overall best rate of BCR-ABLISIS 0.0032% (equivalent to complete molecular response (CMR) was 21% and 17% for nilotinib 300 mg and 400 mg bid (p<0.0001), respectively versus imatinib (6%). The overall best CCyR rate was 85% and 82% for nilotinib 300 mg and 400 mg bid (p<0.001 and p=0.017), respectively, versus imatinib (74%).

The superior efficacy of nilotinib was further demonstrated using the 2009 European Leukemia Net (ELN) 12-month milestone in which fewer patients had suboptimal response or treatment failure on nilotinib 300 mg bid (2%, 3%) and nilotinib 400 mg bid (2%, 2%) versus imatinib (11%, 8%). Rates of progression to AP/BC on treatment were significantly lower for nilotinib 300 mg bid (0.7%, p=0.006) and nilotinib 400 mg bid (0.4%, p=0.003) versus imatinib (4.2%).

The rate of progression on treatment was also significantly lower for nilotinib when including clonal evolution as a criteria for progression. There were fewer CML related deaths on nilotinib 300 mg bid (n=2) and 400 mg bid (n=1) versus imatinib (n=8).

Estimated OS rate (including data from follow-up after discontinuation) at 18 months was significantly higher for nilotinib 400 mg bid (99.3%, p=0.03) versus imatinib (96.9%). Both drugs were well-tolerated. Discontinuations due to adverse events or laboratory abnormalities were lowest for nilotinib 300 mg bid (7%) versus nilotinib 400 mg bid (12%) and imatinib (9%).

With longer follow up there has been minimal change in the occurrence of AEs. The investigators of this study concluded that these data support nilotinib as a new standard of care for patients with newly diagnosed CML.

Reference

ENESTnd Update: Continued Superiority of Nilotinib Versus Imatinib In Patients with Newly Diagnosed Chronic Myeloid Leukemia In Chronic Phase (CML-CP) Abstract 207 presented at 52nd ASH, Orlando, FL, December 4-7, 2010.