What are the efficacy and safety considerations in using ponatinib?

FAQ Library  published on June 10, 2015
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Karen P. Seiter, MD
Professor of Medicine
New York Medical College
Division of Oncology/Hematology
Hawthorne, New York
What are the efficacy and safety considerations in using ponatinib?
Welcome to Managing CML. My name is Karen Seiter, and I am professor of medicine at New York Medical College and director of the Leukemia Service at Westchester Medical Center. I am often asked, “What are the efficacy and safety considerations in using ponatinib?” Ponatinib is a highly potent TKI with activity against a number of kinases including BCR-ABL. Ponatinib was specifically designed to overcome the resistance to the T315I mutation by having a triple carbon‑carbon bond between the purine and methylphenyl groups which allows the drug to bind to the ATP binding pocket without interference. In the PACE trial, complete cytogenetic responses were seen in 48% of patients resistant or intolerant to dasatinib or nilotinib and in 70% of the patients with the T315I mutation. MMR was seen in 31% of patients resistant or intolerant to dasatinib or nilotinib and in 58% of patients with the T315I mutation. However, one year after its accelerated approval by the FDA, a high percentage of vascular events including myocardial infarctions, cerebrovascular events, and venous and arterial thromboses were noted. Additionally, fatal hepatic toxicity was reported in some patients. The FDA quickly withdrew its approval of the drug and halted the ongoing phase 3 EPIC trial which was comparing frontline ponatinib with imatinib. At that time, patients with a T315I mutation had limited access to the drug with an individual IND. However, after reconsideration, the FDA re-approved ponatinib but this time with a more limited indication. The drug is currently approved for the treatment of adult patients with T315I positive CML in chronic phase, accelerated phase, or blast phase or T315I positive Ph-positive ALL, as well as for the treatment of adult patients with chronic phase, accelerated phase or blast phase CML or Ph‑positive ALL for whom no other tyrosine kinase inhibitor therapy is available. As with other therapies, the physician must weigh the potential risks and benefits of therapy for the patient. Thank you for viewing this activity. For additional resources, please view the other educational activities on ManagingCML.com.
Last modified: April 1, 2015
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