Meeting
2012 ASCO Annual Meeting
PACE: A pivotal phase II trial of ponatinib in patients with CML and Ph+ALL resistant or intolerant to dasatinib or nilotinib, or with the T315I mutation.
Authors
Jorge E. Cortes
University of Texas M. D. Anderson Cancer Center, Houston, TX
Jorge E. Cortes , Dong-Wook Kim , Javier Pinilla-Ibarz , Ronald Paquette , Philipp D. le Coutre , Charles Chuah , Franck E. Nicolini , Jane Apperley , Hanna Jean Khoury , Moshe Talpaz , John F DiPersio , Daniel J DeAngelo , Delphine Rea , Elisabetta Abruzzese , Martin C Müller , Michele Baccarani , Carlo Gambacorti-Passerini , Christopher D. Turner , Frank G. Haluska , Hagop Kantarjian
Organizations
University of Texas M. D. Anderson Cancer Center, Houston, TX, The Catholic University of Korea, Seoul, South Korea, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, Ronald Reagan UCLA Medical Center, Los Angeles, CA, Charité University of Medicine Berlin, Berlin, Germany, Singapore General Hospital, Singapore, Singapore, Centre Hospitalier Lyon Sud, Pierre Bénite, France, Hammersmith Hospital, Imperial College London, London, United Kingdom, Emory Winship Cancer Institute, Atlanta, GA, Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, Washington University School of Medicine, St. Louis, MO, Dana-Farber Cancer Institute, Boston, MA, Service des Maladies du Sang, Hopital Saint-Louis, Paris, France, Ematologia e Oncologia, Ospedale S. Eugenio, Rome, Italy, III. Medizinische Klinik, Medizinische Fakultät Mannheim, University of Heidelberg, Mannheim, Germany, University Hospital Bologna, Bologna, Italy, Unità di Ricerca Clinica - Ematologia, Azienda Ospedaliera San Gerardo/University of Milano Bicocca, Monza, Italy, ARIAD Pharmaceuticals, Cambridge, MA
Research Funding
Pharmaceutical/Biotech Company
Background: Ponatinib is a potent, oral, pan-BCR-ABL inhibitor active against the native enzyme and all tested resistant mutants, including the uniformly resistant T315I mutation. Methods: The PACE (Ponatinib Ph+ALL and CML Evaluation) trial started Sept 2010. Pts with refractory CML (CP, AP or BP) or Ph+ALL resistant or intolerant (R/I) to dasatinib or nilotinib or with T315I received 45 mg ponatinib once daily. The trial is ongoing; enrollment completed Sept 2011. Data as of 17 Jan 2012 are reported. Results: 449 pts were enrolled, 5 of whom were ineligible (post-imatinib, non-T315I) but treated. Median age was 59 (18-94) yrs; 53% male. Diagnoses were: 271 CP-CML (R/I=207; T315I=64); 79 AP-CML (R/I=60; T315I=19); 94 BP/ALL (R/I=48; T315I=46). Median time from diagnosis to ponatinib was 6 yrs. Prior TKIs included imatinib (96%), dasatinib (85%), nilotinib (66%), bosutinib (7%); 94% failed ≥2 prior TKIs, 59% failed ≥3 prior TKIs. 83% had a history of resistance to dasatinib or nilotinib; 12% were purely intolerant. In CP, best response to most recent dasatinib or nilotinib was MCyR 25%. Frequent mutations confirmed at entry: 29% T315I, 8% F317L, 4% E255K, 4 % F359V, 3% G250E. Median follow-up was 6.6 months. Response rates are presented in the table. Overall, 64% remained on therapy (77% CP). Most frequent reasons for discontinuation were progression (12%) and AE (10%). Most common drug‑related AEs were thrombocytopenia (33%), rash (33%), dry skin (26%). Conclusions: Ponatinib has substantial activity in heavily pretreated pts and those with refractory T315I. Response rates continue to improve with longer follow-up. Multivariate analyses of predictors of outcome will be presented.
| n Response to ponatinib / N evaluable (%) |
|||
|---|---|---|---|
| Overall | R/I | T315I | |
| CP-CML | |||
| MCyR* | 126/258 (49) | 88/197 (45) | 38/61 (62) |
| CCyR | 105/258 (41) | 70/197 (36) | 35/61 (57) |
| MMR | 68/265 (26) | 40/205 (20) | 28/60 (47) |
| AP-CML | |||
| MHR* | 38/57 (67) | 31/43 (72) | 7/14 (50) |
| MCyR | 27/72 (38) | 18/55 (33) | 9/17 (53) |
| CCyR | 12/72 (17) | 8/55 (15) | 4/17 (24) |
| BP-CML/Ph+ALL | |||
| MHR* | 33/89 (37) | 17/46 (37) | 16/43 (37) |
| MCyR | 30/82 (37) | 14/41 (34) | 16/41 (39) |
| CCyR | 23/82 (28) | 11/41 (27) | 12/41 (29) |
*Primary endpoints: MCyR in CP; MHR in AP, BP/Ph+ALL (baseline MHR excluded).
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Abstract Details
Session Type
Oral Abstract Session
Session Title
Leukemia, Myelodysplasia, and Transplantation
Track
Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
Sub Track
Leukemia
Clinical Trial Registration Number
NCT01207440
Citation
J Clin Oncol 30, 2012 (suppl; abstr 6503)
DOI
10.1200/jco.2012.30.15_suppl.6503
Abstract #
6503
Abstract Disclosures
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