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A novel drug called ponatinib that targets the BCR-ABL mutation overcomes a mutation that has been resistant to all previous approved therapies.
The PACE trial, which is studying a novel drug called ponatinib that targets the BCR-ABL mutation, found that the drug overcomes a mutation that has been resistant to all previous approved therapies. Patients with chronic myeloid leukemia or a type of acute lymphoblastic leukemia whose cancer has the T315I variant of the BCR-ABL mutation typically do not respond to therapy, including the approved tyrosine kinase inhibitors Gleevec (imatinib), Sprycel (dasatinib) and Tasigna (nilotinib).
In the PACE trial, 397 patients with recurrent or resistant CML or BCR-ABL mutation-positive ALL, were given the oral drug once a day continuously. About a fourth of the patients in the study had a confirmed T315I mutation. Most chronic-phase CML patients with the T315I mutation had a noticeable reduction in the number of cancer cells in their blood, a positive result considering that more than half of the patients in the trial had received more than three different types of therapy. Lead researcher Jorge Cortes, MD, explained the effect of ponatinib also extended to patients without the T315I mutation and was seen across all disease stages. Side effects included thrombocytopenia, rash and stomach pains.