Network Meta-Analysis Shows a Significant Advantage of Nilotinib Over Imatinib in Chronic Myeloid Leukemia

This result, covering a patient population of 6314 patients, was reported at the 20th Congress of the European Hematology Society, from June 11 – 14, 2015.

Nicole Skoetz, MD, of the University Hospital of Cologne, Germany, explained that the best treatment strategy for patients with chronic myeloid leukemia is a matter of debate. Since the introduction of the BCR-ABL tyrosine kinase inhibitor imatinib in 1998, patients with chronic myeloid leukemia have experienced a significant improvement in overall survival.

Prior to the tyrosine kinase inhibitors, the 10-year survival rate was 20%; hence imatinib 400 mg is now recommended as standard treatment. Published evidence of second-generation tyrosine kinase inhibitors also recommends dasatinib and nilotinib as first-line therapy. Direct head-to-head comparisons of second-generation tyrosine kinase inhibitors, however, are lacking.

Dr. Skoetz assessed the benefits and risks of different initial treatment strategies including tyrosine kinase inhibitors for patients with chronic myeloid leukemia in the chronic phase.

Sensitive search strategies were developed for CENTRAL, MEDLINE, and conference proceedings from 1990 through 2014. Randomized controlled trials that evaluated a regimen including a first-line tyrosine kinase inhibitor in patients with chronic myeloid leukemia in the chronic phase were reviewed. Two authors independently assessed studies for eligibility.

Data were extracted and the quality of trials assessed in duplicate. The primary outcome measure reviewed was major molecular response. Secondary outcome measures included complete cytogenetic response, overall survival, and adverse events. Specific effect measures were risk ratios for complete major molecular response, complete cytogenetic response, adverse events, and hazard ratios for overall survival.

Data were pooled using network meta-analysis. Direct comparisons within trials were combined with indirect evidence from other trials using a Bayesian random effects model. Both the full network including all trials reporting outcome and a core network including only regimens assessed in at least two trials were evaluated.

Results were reported relative to imatinib 400 mg with a relative risk of 1.85, 1.24 – 2.78, respectively, in the full network meta-analysis. This effect was even more pronounced in the core network with a probability to be superior of 83.1%.

Dasatinib 100 mg (relative risk 1.58, 1.16 – 2.13) and imatinib 800 mg (relative risk 1.45, 1.13 – 1.85) might have been superior to imatinib 400 mg as well. All other treatment strategies and results for complete cytological response showed no statistically significant difference for imatinib 400 mg.

Few events reflecting overall survival were observed and hence results were inconclusive (that is, a wide confidence interval was observed). Results regarding adverse events will be reported in due course. Between-trial heterogeneity was negligible in all three analyses.

Dr. Skoetz concluded that this network meta-analysis comparison of different first-line treatment strategies for treating patients with chronic myeloid leukemia showed a significant nilotinib advantage over standard imatinib 400 mg.

The group’s analysis provided the best available evidence concerning different initial treatment strategies for chronic-phase chronic myeloid leukemia and has contributed valid and important information for both patients and physicians. Some of the regimens reviewed, however, were evaluated in only one trial including a limited number of patients. This limitation may have led to imprecise results.
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