ASCO Annual Meeting 2012
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.
Abstract:
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.