Dr. Jorge Cortes Discusses the Ponatinib PACE Trial

Jorge Cortes, MD, professor and deputy chair, Department of Leukemia, The University of Texas MD Anderson Cancer Center, discusses a pivotal phase II trial that investigated the oral pan-BCR-ABL inhibitor ponatinib for patients with refractory chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphocytic leukemia.

The trial enrolled 449 patients who were resistant or intolerant to dasatinib or nilotinib, or with the T315I mutation. Patients with all phases of CML were enrolled in the trial. Cortes notes that although the goal was to receive patients who had received only prior dasatinib or nilotinib, 94% of patients had failed 2 or more tyrosine kinase inhibitors (TKIs) and 59% had failed 3 or more TKIs, which represented a very heavily pretreated population.

Cortes adds that although the follow-up time is still rather short the responses have been outstanding and will likely continue to improve. For patients with chronic phase CML, major cytogenetic response (MCyR) was observed in 49% of patients and 41% experienced a complete cytogenetic response (CCyR).

The trial yielded impressive results for patients with the T315I mutation, which is uniformly resistant and hard to treat. Overall, patients with this mutation demonstrated a MCyR in 61% of cases and a CCyR in 57%.

Additionally, the response to ponatinib remained strong for patients with more advanced forms of CML. Those with accelerated phase CML demonstrated a 38% MCyR and a major hematologic response (MHR) in 67% of patients and those with blast phase CML showed a 37% MCyR and a 37% MHR.