Comparative efficacy of ponatinib versus the sequential treatment of alternate second generation tyrosine kinase inhibitors in the 3rd line setting

Lipton et al. assessed the efficacy of ponatinib versus the sequential treatment of alternate second generation tyrosine kinase inhibitors (TKIs) in two patient populations, namely 1) post-imatinib and dasatinib and 2) post-imatinib and nilotinib CML patients. This analysis showed that patients treated with ponatinib in this setting had higher complete cytogenetic (CCyR) and major cytogenetic response (MCyR) rates as compared to the sequential use of second generation TKIs.

Lipton and colleagues assessed the efficacy of ponatinib versus sequential treatment of alternate second generation TKIs in the third line treatment of 1) post-imatinib and dasatinib (Ima/Das) and 2) post-imatinib and nilotinib (Ima/Nil) CML patients. A total of 6 studies evaluating bosutinib, nilotinib and ponatinib were included for the Ima/Das group (n= 419) together with 5 studies evaluating bosutinib, dasatinib and ponatinib for the Ima/Nil group (n=83).

Synthesized treatment-specific probabilities of CCyR in the Ima/Das group were 20% for bosutinib, 27% for nilotinib, and 54% for ponatinib (see also ‘Key slides’). Treatment-specific probabilities of MCyR in the Ima/Das group were 28% for bosutinib, 41% for nilotinib, and 66% for ponatinib.

Synthesized treatment-specific probabilities of CCyR for the group Ima/Nil were 26% for bosutinib, 25% for dasatinib, and 67% for ponatinib, while treatment-specific probabilities of MCyR for the group Ima/Nil were 33% for bosutinib and 75% for ponatinib. In summary, in this analysis overall response rates appeared to be higher for TKIs in the post imatinib and nilotinib group compared with the post imatinib and dasatinib group. For both groups however, patients on ponatinib had higher CCyR and MCyR rates as compared to the sequential second generation TKIs included in this analysis. However, it is to be noted that this analysis had some important limitations including the fact that the post imatinib and dasatinib group contained more studies with larger sample sizes, the significant heterogeneity between the studies in the analysis, and the variation in follow-up between the studies.

Reference

Lipton JH, Shah D, Tongbram V, et al. Comparative Efficacy Among 3rd Line Post-Imatinib Chronic Phase-Chronic Myeloid Leukemia (CP-CML) Patients after Failure of Dasatinib or Nilotinib Tyrosine Kinase Inhibitors. Presented at ASH 2014; Abstract #4551.