Nilotinib Superior to Imatinib, Fewer Mutations in Treatment of CML-CP

CHICAGO—Two studies presented at the American Society of Clinical Oncology's 2011 Annual Meeting showed that nilotinib demonstrated greater efficacy and notably improved disease control over imatinib in the treatment of patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP), as well as fewer mutations as compared with imatinib.

Richard A. Larson, MD, from the University of Chicago Medical Center, and colleagues reported on the 24-month follow-up results of the ENESTnd trial (at the 12-month point, nilotinib demonstrated superiority over imatinib). The trial included 846 CML-CP patients who were randomized to receive nilotinib 300mg twice daily (n=282), nilotinib 400mg twice daily (n=281), or imatinib 400mg once daily (n=283). At 12 months, the primary endpoint was major molecular response (MMR). At Month 24, response rates were significantly higher for nilotinib. MMR rates remained superior for nilotinib across all Sokal risk groups (ie, older age; enlarged spleen; higher platelet count; higher peripheral blast percentage). See Figure 1.

As at the 12 month point, there continued to be significantly fewer progressions to AP/BC on treatment at Month 24, including clonal evolution (CE), on nilotinib 300mg (n=2) and 400mg (n= 5) than imatinib (n=17).See Figure 2. Progression-free survival (PFS) was significant for the nilotinib 400mg arm, estimated 24-month PFS=97.7% (P=0.0437). While the rates of PFS were similar for the other arms, the results were nonsignificant. Also at the 24-month mark, overall survival remained similar in all groups, but there were fewer CML-related deaths on both nilotinib 300mg (n=5) and 400mg (n=3) than in the imatinib group (n=10). Both drugs were well tolerated.

Discontinuation due to adverse events/laboratory abnormalities was 9% for nilotinib 300mg, 13% for nilotinib 400mg, and 10% for imatinib. Giuseppi Saglio, MD, of the University of Turin, Italy, and colleagues reported on mutation incidence in the ENESTnd trial, stating that the baseline (BL) BCR-ABL mutation status and emergence of new mutations with minimum 24-month follow-up showed that new mutations were higher for imatinib. Mutation testing was performed in patients who failed to reach MMR at 12 months by direct sequencing of the kinase domain in a central laboratory at: BL, fivefold increase in PCR levels,