{"entity":{"id":"paper-pace-ponatinib-nejm-2013","kind":"paper","name":"PACE: ponatinib in Philadelphia chromosome-positive leukaemias resistant to earlier tyrosine kinase inhibitors","aka":[],"tldr":"Ponatinib produced deep responses in patients with chronic myeloid leukaemia or Philadelphia-positive acute lymphoblastic leukaemia whose disease had resisted other kinase inhibitors, including the T315I mutation that no other drug could reach.","summary":"Phase 2 study of 449 heavily pretreated patients with chronic, accelerated or blast-phase CML or Ph-positive ALL, including 128 with the T315I gatekeeper mutation, treated with ponatinib 45 mg daily.\n\nIn chronic phase, 56 percent achieved a major cytogenetic response (70 percent of those with T315I); responses in accelerated and blast phase were lower and shorter. Arterial occlusive events emerged as the defining toxicity, later prompting dose reduction strategies.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2013","url":"https://doi.org/10.1056/NEJMoa1306494"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24180494/"}],"tags":[],"related":[],"cancers":["cml-advanced-phase"],"sections":[],"technologies":[],"targets":[],"drugs":["ponatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2013,"doi":"10.1056/NEJMoa1306494","pmid":"24180494","authors":"Cortes JE, Kim DW, Pinilla-Ibarz J, et al.","paperType":"observational","findings":["Major cytogenetic response in 56 percent of chronic-phase patients and 70 percent of those with T315I.","Major haematological response in 55 percent of accelerated-phase and 31 percent of blast-phase or Ph-positive ALL patients."],"whatItMeans":"Ponatinib is the drug for T315I-mutated disease and for patients who have failed several inhibitors, including in accelerated and blast phase as a bridge to transplant. Cardiovascular risk must be managed actively.","caveats":["Serious arterial thrombotic events in a substantial minority, increasing with time on treatment.","Single-arm design; response-based dose reduction (OPTIC) came later."],"changedPractice":true,"participants":449},"route":"/key-papers/paper-pace-ponatinib-nejm-2013/","neighbours":{"cancer":[{"id":"cml-advanced-phase","kind":"cancer","name":"Chronic myeloid leukaemia, accelerated and blast phase","route":"/cancers/cml-advanced-phase/"}],"drug":[{"id":"ponatinib","kind":"drug","name":"Ponatinib","route":"/drugs/ponatinib/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}