Ariad Pharmaceuticals Inc fka ARIA

[LUMA14]

Dasatinib, Nilotinib, Ponatinib Increase Vascular Occlusive Events

link to article

BCR-ABL tyrosine kinase inhibitors (TKI) dasatinib, nilotinib, and ponatinib, used in the treatment of patients with chronic myeloid leukemia (CML) increase vascular occlusive events, a study published in JAMA Oncology has shown.1

A phase 3 trial evaluating ponatinib in patients with CML was interrupted due to a noteworthy increase in vascular occlusive events. Because a similar risk was also suspected with nilotinib, investigators sought to assess the risk of vascular occlusive events in patients with CML treated by new generations of TKIs, as well as examine each TKI's clinical benefit.

For the systematic review, researchers identified 249 abstracts, of which 10 met eligibility criteria. Those 10 randomized clinical trials included a total of 3043 patients.

Results showed that the risk of vascular occlusive events was increased with dasatinib (OR, 3.86; 95% CI: 1.33-11.18), nilotinib (OR, 3.42; 95% CI: 2.07-5.63), and ponatinib (OR, 3.47; 95% CI: 1.23-9.78) compared with imatinib. There was no significant difference in vascular occlusive events between bosutinib and imatinib (OR, 2.77; 95% CI: 0.39-19.77).

In terms of clinical benefit, researchers found that new-generation TKIs increased the rate of major molecular response at 1 year compared with imatinib (OR, 2.22; 95% CI: 1.87-2.63), but there was no statistically significant difference in 1-year overall survival (OR, 1.20; 95% CI: 0.63-2.29).

The authors note that the inability to access individual and time-to-event data and the differences in evaluation criteria between studies may have introduced bias to their meta-analysis.

REFERENCE

1. Douxfils J, Haguet H, Mullier F, et al. Association between BCR-ABL tyrosine kinase inhibitors for chronic myeloid leukemia and cardiovascular events, major molecular response, and overall survival: A systematic review and meta-analysis [published online ahead of print February 4, 2015]. JAMA Onco. doi:10.1001/jamaoncol.2015.5932.

link to Abstact

Looking on the data of the used studies and patients might be interesting. So discussion among the docs may start.