LONG-TERM EFFICACY AND SAFETY OF PONATINIB IN HEAVILY PRETREATED LEUKEMIA PATIENTS: 4-YEAR RESULTS FROM THE PIVOTAL PHASE 2 PACE TRIAL
Author(s): ,
Jorge E Cortes
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston, TX,United States
,
Javier Pinilla-Ibarz
Affiliations:
H. Lee Moffitt Cancer Center & Research Institute,Tampa, FL,United States
,
Philipp D le Coutre
Affiliations:
Charité Universitätsmedizin Berlin,Berlin,Germany
,
Ronald Paquette
Affiliations:
Ronald Reagan UCLA Medical Center, University of California,Los Angeles, CA,United States
,
Charles Chuah
Affiliations:
Singapore General Hospital and Duke-National University of Singapore Graduate Medical School,Singapore,Singapore
,
Franck E Nicolini
Affiliations:
Centre Hospitalier Lyon Sud, Pierre Bénite,Lyon,France
,
Jane F Apperley
Affiliations:
Centre for Haematology,Imperial College,London,United Kingdom
,
H Jean Khoury
Affiliations:
Winship Cancer Institute of Emory University,Atlanta, GA,United States
,
Moshe Talpaz
Affiliations:
Comprehensive Cancer Center,University of Michigan,Ann Arbor, MI,United States
,
Michele Baccarani
Affiliations:
S. Orsola-Malpighi University Hospital,Bologna,Italy
,
Stephanie Lustgarten
Affiliations:
ARIAD Pharmaceuticals, Inc.,Cambridge, MA,United States
,
Frank G Haluska
Affiliations:
ARIAD Pharmaceuticals, Inc.,Cambridge, MA,United States
,
François Guilhot
Affiliations:
Inserm CIC 1402, CHU de Poitiers,Poitiers,France
,
Michael W Deininger
Affiliations:
Huntsman Cancer Institute, University of Utah,Salt Lake City, UT,United States
,
Andreas Hochhaus
Affiliations:
Jena University Hospital, Jena,Germany
,
Timothy P Hughes
Affiliations:
Institute of Medicine and Veterinary Science,Adelaide,Australia
,
Neil P Shah
Affiliations:
University of California San Francisco,San Francisco, CA,United States
Hagop M Kantarjian
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston, TX,United States
EHA Library. Cortes J. 06/10/16; 133215; P228
Dr. Jorge Cortes
Dr. Jorge Cortes
Contributions
Abstract
Abstract: P228

Type: Poster Presentation

Presentation during EHA21: On Friday, June 10, 2016 from 17:15 - 18:45

Location: Poster area (Hall H)

Background
The approved tyrosine kinase inhibitor (TKI) ponatinib is potently active against native and resistant BCR-ABL, including T315I. 

Aims
The pivotal phase 2 PACE trial (NCT01207440) evaluated the efficacy and safety of ponatinib.

Methods
Patients with chronic myeloid leukemia (CML) or Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL) refractory to dasatinib or nilotinib, or with T315I, were enrolled in PACE (starting dose 45 mg once daily). All patients gave informed consent. Dose reductions were recommended in October 2013 due to observed arterial occlusive events (AOEs). Efficacy and safety at 4 years, as well as by year for chronic phase (CP) CML patients are reported (data as of 3 August, 2015). Exposure-adjusted incidence rates of new AOEs are reported as the number of events/100 patient-years.

Results
Of 449 patients, 59% received ≥3 prior TKIs. At analysis, 30% (133/449) of patients (median follow-up 37.3, range 0.1–58.5 months) and 41% (110/270) of CP-CML pts (48.2, 0.1–58.5 months) remained on study. Primary reasons for discontinuation were disease progression (22.5% overall, 10.4% CP-CML) and adverse events (AEs) (16.0% overall, 18.5% CP-CML).  Responses continued to deepen over time (Table, CP-CML patients) despite dose reductions. Among CP-CML patients, estimated 4-year rates for PFS, OS, and maintenance of major cytogenetic response (MCyR) and major molecular response (MMR) were 56%, 77%, 82% and 61%, respectively. For accelerated phase patients, the estimated 4-year OS was 51%; median OS for blast phase/Ph+ALL patients was 6.9 months (95% CI, 5.0-9.2). Common (in ≥30% of patients) treatment-emergent AEs were thrombocytopenia 44%, abdominal pain 43%, rash 42%, constipation 37%, headache 37%, dry skin 36%, fatigue and hypertension 30%. AOE rate/serious AOE rate was 23%/19%, including cardio- 13%/9%, cerebro- 9%/7%, and peripheral-vascular 9%/7%. Of patients with AOEs (n=104), 38% remained on study. Exposure-adjusted incidence rates of new AOEs fell after the first 2 years: 15.5 Year 1, 15.7 Year 2, 10.4 Year 3, and 9.6 Year 4. Nearly 2 years after recommended dose reductions, 87% (114/131) and 74% (70/95) of CP-CML pts were estimated to maintain MCyR and MMR, respectively, and 8% (6/75) of all dose-reduced pts without a prior AOE on trial had an AOE. 

Conclusion
After 4 years, heavily pretreated patients continue to show deep and lasting responses on ponatinib, and approximately 2 years post recommended dose reductions, maintenance of response is high, and the incidence of newly occurring AOEs has decreased. 



Session topic: Chronic myeloid leukemia - Clinical 1

Keyword(s): Chronic myeloid leukemia, Clinical trial, Tyrosine kinase inhibitor

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