TY - JOUR
T1 - Ponatinib efficacy and safety in Philadelphia chromosome–positive leukemia
T2 - final 5-year results of the phase 2 PACE trial
AU - Cortes, Jorge E.
AU - Kim, Dong Wook
AU - Pinilla-Ibarz, Javier
AU - le Coutre, Philipp D.
AU - Paquette, Ronald
AU - Chuah, Charles
AU - Nicolini, Franck E.
AU - Apperley, Jane F.
AU - Khoury, H. Jean
AU - Talpaz, Moshe
AU - DeAngelo, Daniel J.
AU - Abruzzese, Elisabetta
AU - Rea, Delphine
AU - Baccarani, Michele
AU - Müller, Martin C.
AU - Gambacorti-Passerini, Carlo
AU - Lustgarten, Stephanie
AU - Rivera, Victor M.
AU - Haluska, Frank G.
AU - Guilhot, François
AU - Deininger, Michael W.
AU - Hochhaus, Andreas
AU - Hughes, Timothy P.
AU - Shah, Neil P.
AU - Kantarjian, Hagop M.
N1 - Publisher Copyright:
Copyright 2011 by The American Society of Hematology; all rights reserved.
PY - 2018/7/26
Y1 - 2018/7/26
N2 - Ponatinib has potent activity against native and mutant BCR-ABL1, including BCR-ABL1T315I. The pivotal phase 2 Ponatinib Ph1 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 5 270) 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.
AB - Ponatinib has potent activity against native and mutant BCR-ABL1, including BCR-ABL1T315I. The pivotal phase 2 Ponatinib Ph1 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 5 270) 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.
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U2 - 10.1182/blood-2016-09-739086
DO - 10.1182/blood-2016-09-739086
M3 - Article
C2 - 29567798
AN - SCOPUS:85048250671
SN - 0006-4971
VL - 132
SP - 393
EP - 404
JO - Blood
JF - Blood
IS - 4
ER -