Ponatinib treatment was compared with imatinib in newly diagnosed patients with chronic myeloid leukemia in chronic phase (CP-CML), but efficacy could not be assessed due to trial termination, according to a study published in the journal The Lancet Oncology.1

Ponatinib has demonstrated potent activity against treatment-resistant CML despite the kinase inhibitor’s association with arterial occlusion. Researchers sought to investigate whether this activity and safety profile would improve outcomes vs imatinib in previously untreated patients with CML.

For the international, open-label, phase 3 EPIC trial, researchers enrolled 307 patients with newly diagnosed Philadelphia chromosome-positive CP-CML. Participants were randomly assigned 1:1 to receive ponatinib 45 mg orally once daily or imatinib 400 mg orally once daily until disease progression or unacceptable toxicity.

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After concerns of vascular adverse events observed in patients given ponatinib in other trials, the EPIC trial was terminated early, thereby limiting the evaluation of the primary endpoint of major molecular response at 12 months.

Results showed that 80% of the 10 evaluable ponatinib-treated patients achieved a major molecular response at 12 months compared with 38% of the 13 evaluable patients given imatinib (P = .074).

In regard to safety, 7% of the 154 patients who received ponatinib and 2% of the 152 imatinib-treated patients experienced arterial occlusive events (P = .052). Ten cases in the ponatinib arm and 1 in the imatinib group were deemed to be serious (P = .010).

The most common treatment-related grade 3 or 4 adverse events in the ponatinib arm were increased lipase, thrombocytopenia, and rash. Neutropenia and thrombocytopenia were the most frequently reported grade 3 or 4 imatinib-related adverse events.

Because the EPIC trial was terminated early, efficacy of ponatinib in this treatment setting remains to be established; however, preliminary data suggest there may be a benefit, but with more arterial occlusive events than with imatinib.


1. Lipton JH, Chuah C, Guerci-Bresler A, et al. Ponatinib versus imatinib for newly diagnosed chronic myeloid leukaemia: an international, randomised, open-label, phase 3 trial [published online ahead of print April 12, 2016]. Lancet Oncol. doi:10.1016/S1470-2045(16)00080-2.