Nilotinib, a second generation tyrosine-kinase inhibitor (TKI), reduces the proliferation of BCR-ABL positive chronic myeloid leukemia (CML) cells by inhibiting the BCR-ABL pathway. Since 2007 nilotinib is approved for the 2nd-line therapy of Philadelphia chromosome (Ph+) CML patients in Europe. In September 2010, the EMA granted a positive opinion for the approval of nilotinib for the 1st-line therapy of Ph+ CML in the chronic phase.
The pivotal ENESTnd trial investigated whether nilotinib 300mg or 400mg is more effective as 1st-line therapy in Ph+ CML-CP patients than the current standard of care – imatinib 400mg.
The results of the trial indicate that nilotinib is clinically more effective than imatinib. The rate of major molecular response, the primary endpoint, is 66% (p<0.001) and 62% (p<0.001) in the nilotinib 300mg and 400mg groups respectively in comparison to 40% in the imatinib group. Progression to the accelerated phase or blast crisis occurred more frequent in the control group (4.2%) compared to nilotinib 300mg (0.7%) and nilotinib 400mg (1.2%). The safety profile of these two agents was comparable and is considered to be clinically manageable and acceptable.
Despite these first encouraging interim results, further follow-up is essential to provide information on durability of the responses, quality-of- life and to further investigate the safety profile of nilotinib in the 1st-line therapy of CML.