Targeted therapy for patients with chronic myeloid leukemia: clinical trial experience and challenges in inter-trial comparisons.

The treatment of chronic myeloid leukemia (CML) was revolutionized by the introduction of the targeted tyrosine kinase inhibitor (TKI) imatinib mesylate. Later, to improve efficacy and tolerability, the more potent TKIs dasatinib and nilotinib were evaluated in CML. Clinicians comparing the clinical efficacy of TKIs face considerable challenges, including the variable treatment histories of patients receiving second-line therapy. The aim of this review is to highlight the pitfalls and possible solutions for comparing efficacy across disparate CML trials. Comparison of efficacy across trials is aided by careful consideration of possible confounding factors, including treatment history, definitions of imatinib intolerance or resistance, and BCR-ABL mutational status at baseline. However, methods exist to improve the comparability of data from different trials, yielding a more clinically and statistically meaningful inter-trial comparison.