Jorge E. Cortes, MD, Department of Leukemia, University of Texas, MD Anderson Cancer Center, describes results from a 12 month follow up of the phase II PACE study that examined the potent, oral, pan-BCR-ABL inhibitor ponatinib in patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).

The PACE trial enrolled 449 patients who were resistant or intolerant (R/I) to dasatinib or nilotinib, or with the T315I mutation.

In the trial, patients were stratified into 6 cohorts based on disease stage and mutation status. In the chronic phase (CP)-CML cohort the endpoint was major cytogenetic response (MCyR). For those with accelerated phase (AP)-CML, blast phase (BP)-CML, and Ph+ ALL the endpoint was major hematologic response (MHR).

Overall, 271 patients were stratified to the CP-CML cohort. A MCyR was observed in 56% of the patients who were R/I to dasatinib or nilotinib and 70% with T315I mutation. Additionally, complete cytogenetic response was seen in 46%.

The AP-CML cohort contained 79 patients and showed similar response rates to those with CP-CML. Overall, 57% of R/I patients and 50% of patients harboring T315I mutations experienced a MHR. Among the 94 patients with BP-CML and Ph+ALL, MHR was observed in 35% of those R/I and 33% with T315I mutations. Five patients were treated but did not qualify for any of the cohorts.

Cortes says that ponatinib was well tolerated in the trial and had significant activity in heavily pretreated patients with CML and Ph+ ALL. Overall, this agent showed success in an area where patients have limited treatment options.

On December 14, 2012, the FDA approved ponatinib based on information from the PACE trial (Find out more).