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Ref Type Journal Article
PMID (23935038)
Authors Frankfurt O, Licht JD
Title Ponatinib--a step forward in overcoming resistance in chronic myeloid leukemia.
Journal Clinical cancer research : an official journal of the American Association for
Vol 19
Issue 21
Date 2013 Nov 1
URL
Abstract Text With the current therapy, the improvement in survival of patient with early chronic phase chronic myelogenous leukemia (CML) is unrivaled by that of any other leukemia. In fact, extrapolation of the survival curves may suggest that life expectancy of patients who achieve and maintain predetermined milestones may not differ from that of the age-matched healthy adults. The main reasons for such success are the presence of a well-defined molecular target, the BCR-ABL oncogene, necessary and sufficient for the initiation and propagation of CML, and the powerful and selective agents that inhibit it. Five U.S. Food and Drug Administration (FDA)-approved tyrosine kinase inhibitors (TKI), each with unique activities and toxicity profiles, allow for individualized patient care. Despite the remarkable responses of most patients, a small but significant fraction of patients develops clinical resistance to the TKIs, some of which is attributed to the BCR-ABL kinase domain mutations affecting TKI binding and activity. The recently approved third-generation TKI ponatinib showed remarkable activity in the patients with multi-TKI-resistant disease. Particularly impressive was its efficacy in patients with T315I mutation that is resistant to all other TKIs. In lieu of the current emphasis on achieving earlier and more profound responses and excellent activity of ponatinib in the refractory setting, its optimal position among the available armamentarium of agents is being established.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown chronic myeloid leukemia not applicable Ponatinib FDA approved Actionable In a Phase II clinical trial which supported FDA approval, Iclusig (ponatinib) was effective in promoting disease regression in 52% of patients with accelerated phase chronic myeloid leukemia, 31% of patients with blast phase chronic myeloid leukemia, and 41% of patients with Philadelphia chromosome positive acute lymphoblastic leukemia (PMID: 23935038). 23935038 detail...
Unknown unknown lymphoid leukemia not applicable Ponatinib FDA approved Actionable In a Phase II clinical trial which supported FDA approval, Iclusig (ponatinib) was effective in promoting disease regression in 52% of patients with accelerated phase chronic myeloid leukemia, 31% of patients with blast phase chronic myeloid leukemia, and 41% of patients with Philadelphia chromosome positive acute lymphoblastic leukemia (PMID: 23935038). 23935038 detail...