PONATINIB EFFICACY AND SAFETY IN HEAVILY PRETREATED LEUKEMIA PATIENTS: 3-YEAR RESULTS OF THE PACE TRIAL
EHA Library. Cortes J. Jun 12, 2015; 100486; P234
Disclosure(s): The University of Texas MD Anderson Cancer Center
Dr. Jorge Cortes
Contributions
Contributions
Abstract
Abstract: P234
Type: Poster Presentation
Presentation during EHA20: From 12.06.2015 17:15 to 12.06.2015 18:45
Location: Poster area (Hall C)
Background
Ponatinib is an approved oral tyrosine kinase inhibitor (TKI) with potent activity against native BCR-ABL and resistant mutants, including the T315I mutant.
Aims
The phase 2 PACE trial evaluated the efficacy and safety of ponatinib (starting dose 45 mg once daily).
Methods
Patients with chronic myeloid leukemia (CML) or Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) resistant/intolerant to dasatinib/nilotinib or with T315I were enrolled in PACE (NCT01207440) and gave informed consent. Of 449 patients, 58% received ≥3 prior TKIs. Arterial occlusive events (AOEs) led to recommended dose reduction in October 2013. Exposure-adjusted incidence rates of new AOEs were calculated as (number of first events in interval)/(total exposure for interval in patient-years) x 100. Rates for later intervals exclude patients with prior events.
Results
As of October 6, 2014: 33% of all patients and 45% of chronic-phase (CP)-CML patients remained on study. Median follow-up was 34.2 (0.1–48.6) months overall and 38.4 (0.1–48.6) months for CP-CML patients. Main reasons for discontinuation were progression (21% overall, 9% CP-CML) and adverse events (AEs) (15% overall, 17% CP-CML). Among CP-CML patients, 59% achieved major cytogenetic response (MCyR), 39% achieved major molecular response (MMR) or better, and 22% achieved MR4.5. Responses were durable, with an estimated 83% of responders maintaining MCyR at 3 years; estimated rates of progression-free survival and overall survival at 3 years were 61% and 82%, respectively. Among accelerated-phase CML, blast-phase CML, and Ph+ ALL patients, estimated rates of overall survival at 3 years were 59%, 9%, and 16%, respectively. Treatment-emergent AEs in ≥25% of patients were thrombocytopenia (43%), abdominal pain (42%), rash (41%), constipation (37%), headache (37%), dry skin (36%), fatigue (30%), pyrexia (29%), arthralgia (29%), hypertension (28%), nausea (28%), and neutropenia (25%). Rates of AOEs (any/serious) were 22%/17%, including cardiovascular (12%/8%), cerebrovascular (8%/6%), and peripheral vascular (8%/6%) events. Rates of venous thromboembolic events (VTEs; any/serious) were 5%/4%. Of the 99 patients with AOEs, 42 remained on study and 33 were still in MCyR. Exposure-adjusted incidence rates of new AOEs (events per 100 patient-years) were 14.5 in Year 1, 14.1 in Year 2, and 10.8 in Year 3. Exposure-adjusted incidence rates of new VTEs (events per 100 patient-years) were 3.5 in Year 1, 1.8 in Year 2, and 1.8 in Year 3. One year after recommended dose reduction, 61 (95%) of 64 CP-CML patients maintained MCyR, 44 (94%) of 47 CP-CML patients maintained MMR, and 5 (7%) of 70 ongoing patients without a prior AOE had an AOE.
Summary
Ponatinib continues to provide deep, durable responses in heavily pretreated patients, particularly those with CP-CML. One year after recommended dose reduction, responses were maintained and incidence of new AOEs was low. A dose-ranging trial of ponatinib in refractory CML to evaluate benefits and risks is currently planned.
Keyword(s): Chronic myeloid leukemia, Tyrosine kinase inhibitor
Session topic: Chronic myeloid leukemia - Clinical 1
Type: Poster Presentation
Presentation during EHA20: From 12.06.2015 17:15 to 12.06.2015 18:45
Location: Poster area (Hall C)
Background
Ponatinib is an approved oral tyrosine kinase inhibitor (TKI) with potent activity against native BCR-ABL and resistant mutants, including the T315I mutant.
Aims
The phase 2 PACE trial evaluated the efficacy and safety of ponatinib (starting dose 45 mg once daily).
Methods
Patients with chronic myeloid leukemia (CML) or Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) resistant/intolerant to dasatinib/nilotinib or with T315I were enrolled in PACE (NCT01207440) and gave informed consent. Of 449 patients, 58% received ≥3 prior TKIs. Arterial occlusive events (AOEs) led to recommended dose reduction in October 2013. Exposure-adjusted incidence rates of new AOEs were calculated as (number of first events in interval)/(total exposure for interval in patient-years) x 100. Rates for later intervals exclude patients with prior events.
Results
As of October 6, 2014: 33% of all patients and 45% of chronic-phase (CP)-CML patients remained on study. Median follow-up was 34.2 (0.1–48.6) months overall and 38.4 (0.1–48.6) months for CP-CML patients. Main reasons for discontinuation were progression (21% overall, 9% CP-CML) and adverse events (AEs) (15% overall, 17% CP-CML). Among CP-CML patients, 59% achieved major cytogenetic response (MCyR), 39% achieved major molecular response (MMR) or better, and 22% achieved MR4.5. Responses were durable, with an estimated 83% of responders maintaining MCyR at 3 years; estimated rates of progression-free survival and overall survival at 3 years were 61% and 82%, respectively. Among accelerated-phase CML, blast-phase CML, and Ph+ ALL patients, estimated rates of overall survival at 3 years were 59%, 9%, and 16%, respectively. Treatment-emergent AEs in ≥25% of patients were thrombocytopenia (43%), abdominal pain (42%), rash (41%), constipation (37%), headache (37%), dry skin (36%), fatigue (30%), pyrexia (29%), arthralgia (29%), hypertension (28%), nausea (28%), and neutropenia (25%). Rates of AOEs (any/serious) were 22%/17%, including cardiovascular (12%/8%), cerebrovascular (8%/6%), and peripheral vascular (8%/6%) events. Rates of venous thromboembolic events (VTEs; any/serious) were 5%/4%. Of the 99 patients with AOEs, 42 remained on study and 33 were still in MCyR. Exposure-adjusted incidence rates of new AOEs (events per 100 patient-years) were 14.5 in Year 1, 14.1 in Year 2, and 10.8 in Year 3. Exposure-adjusted incidence rates of new VTEs (events per 100 patient-years) were 3.5 in Year 1, 1.8 in Year 2, and 1.8 in Year 3. One year after recommended dose reduction, 61 (95%) of 64 CP-CML patients maintained MCyR, 44 (94%) of 47 CP-CML patients maintained MMR, and 5 (7%) of 70 ongoing patients without a prior AOE had an AOE.
Summary
Ponatinib continues to provide deep, durable responses in heavily pretreated patients, particularly those with CP-CML. One year after recommended dose reduction, responses were maintained and incidence of new AOEs was low. A dose-ranging trial of ponatinib in refractory CML to evaluate benefits and risks is currently planned.
Keyword(s): Chronic myeloid leukemia, Tyrosine kinase inhibitor
Session topic: Chronic myeloid leukemia - Clinical 1
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