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Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial

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Title: Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial
Authors: Cortes, JE
Kim, D-W
Pinilla-Ibarz, J
Le Coutre, PD
Paquette, R
Chuah, C
Nicolini, FE
Apperley, JF
Khoury, HJ
Talpaz, M
DeAngelo, DJ
Abruzzese, E
Rea, D
Baccarani, M
Mueller, MC
Gambacorti-Passerini, C
Lustgarten, S
Rivera, VM
Haluska, FG
Guilhot, F
Deininger, MW
Hochhaus, A
Hughes, TP
Shah, NP
Kantarjian, HM
Item Type: Journal Article
Abstract: Ponatinib has potent activity against native and mutant BCR-ABL1, including BCR-ABL1T315I. The pivotal phase 2 Ponatinib Ph+ ALL and CML Evaluation (PACE) trial evaluated efficacy and safety of ponatinib at a starting dose of 45 mg once daily in 449 patients with chronic myeloid leukemia (CML) or Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL) resistant/intolerant to dasatinib or nilotinib, or with BCR-ABL1T315I. This analysis focuses on chronic-phase CML (CP-CML) patients (n = 270) with 56.8-month median follow-up. Among 267 evaluable patients, 60%, 40%, and 24% achieved major cytogenetic response (MCyR), major molecular response (MMR), and 4.5-log molecular response, respectively. The probability of maintaining MCyR for 5 years was 82% among responders. Dose reductions were implemented in October 2013 to decrease the risk of arterial occlusive events (AOEs); ≥90% of CP-CML patients who had achieved MCyR or MMR maintained response 40 months after elective dose reductions. Estimated 5-year overall survival was 73%. In CP-CML patients, the most common treatment-emergent adverse events were rash (47%), abdominal pain (46%), thrombocytopenia (46%), headache (43%), dry skin (42%), and constipation (41%). The cumulative incidence of AOEs in CP-CML patients increased over time to 31%, while the exposure-adjusted incidence of new AOEs (15.8 and 4.9 per 100 patient-years in years 1 and 5, respectively) did not increase over time. These final PACE results demonstrate ponatinib provides durable and clinically meaningful responses, irrespective of dose reductions, in this population of heavily pretreated CP-CML patients. This trial was registered at www.clinicaltrials.gov as #NCT01207440.
Issue Date: 26-Jul-2018
Date of Acceptance: 7-Mar-2018
URI: http://hdl.handle.net/10044/1/62990
DOI: https://dx.doi.org/10.1182/blood-2016-09-739086
ISSN: 0006-4971
Publisher: American Society of Hematology
Start Page: 393
End Page: 404
Journal / Book Title: BLOOD
Volume: 132
Issue: 4
Copyright Statement: © 2018 by The American Society of Hematology.
Keywords: Science & Technology
Life Sciences & Biomedicine
Hematology
CHRONIC MYELOID-LEUKEMIA
TYROSINE KINASE INHIBITOR
CHRONIC MYELOGENOUS LEUKEMIA
BCR-ABL INHIBITOR
IMATINIB-RESISTANT
ADVERSE EVENTS
CML PATIENTS
DASATINIB
NILOTINIB
RECOMMENDATIONS
1102 Cardiovascular Medicine And Haematology
1103 Clinical Sciences
1114 Paediatrics And Reproductive Medicine
Immunology
Publication Status: Published
Online Publication Date: 2018-07-26
Appears in Collections:Department of Medicine
Faculty of Medicine



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