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Ponatinib shows promise for chronic myeloid leukemia in chronic phase
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Ponatinib conferred durable, clinically meaningful responses among patients with chronic myeloid leukemia in chronic phase who did not respond to other treatments, according to findings from the phase 2 PACE trial.
“The PACE trial is among the longest and largest studies of patients with chronic phase chronic myeloid leukemia who have received two or three prior tyrosine kinase inhibitors, and the findings provide treating physicians with important updated information about the clinical benefits and safety profile of Iclusig [Ponatinib, Takeda Pharmaceutical],” Jorge Eduardo Cortes, MD, deputy chair and professor of medicine in the department of leukemia at The University of Texas MD Anderson Cancer Center, said in a press release. “These final PACE results demonstrate that Iclusig provides lasting clinically meaningful responses, irrespective of dose reductions, in this population.”
The analysis included 449 patients with CML or Philadelphia chromosome-positive acute lymphoblastic leukemia that was resistant or intolerant to nilotinib (Tasigna, Novartis) or dasatinib, or who had a BRC-ABL1T315l mutation. More than 90% of patients had previously been treated with at least two TKIs.
Patients received daily ponatinib at a starting dose of 45 mg once daily.
Researchers conducted a subgroup analysis of 267 evaluable patients out of 270 with CML in chronic phase.
Median follow-up was 56.8 months.
Sixty percent of patients in this population achieved major cytogenetic response, 40% achieved major molecular response and 24% achieved molecular response.
Most patients (82%) who achieved major cytogenic response at 1 year were expected to maintain their responses at 5 years, as were most patients (59%) who achieved major molecular response.
In October 2013, the researchers implemented dose reductions to reduce risk for arterial occlusive events.
The vast majority of patients (> 90%) who achieved either major cytogenic or major molecular response maintained their responses at the 40-month mark even after reducing dosage, including dosage reduced to 15 mg per day.
Serious adverse events that occurred among 5% or more of this population included pancreatitis (7%), atrial fibrillation (6%) pneumonia (6%) and angina pectoris (5%).
Serious adverse events that occurred among 5% or more of the overall population included pneumonia (7%) and pancreatitis (6%). Atrial fibrillation occurred among 4% of the overall population, and angina pectoris occurred among 3%.
The most common treatment-emergent adverse events of any grade among patients with CML in chronic phase included rash (47%), abdominal pain (46%), thrombocytopenia (46%), headache (43%), dry skin (42%) and constipation (41%). The most common treatment-emergent grade 3 or grade 4 adverse events among these patients included thrombocytopenia (35%), neutropenia (17%), hypertension (14%), increased lipase (13%), abdominal pain (10%) and anemia (10%).
The incidence of arterial occlusive events rose over time. Nearly one-third of patients with CML in chronic phase (31%) and one-fourth of the overall population (25%) reported at least one such event.
“These final results of the PACE study support ponatinib as an effective treatment for patients with CML who have received prior therapies,” the researchers wrote. “The decision to initiate ponatinib therapy should be guided by carefully weighing the risk-benefit ratio for each patient, particularly in those who may be at increased risk [for] arterial occlusive events.” – by Andy Polhamus
Disclosures: Cortes reports research funding from Ariad, Bristol-Myers Squibb, Novartis, Pfizer and Teva; and consulting roles with Ariad, Bristol-Myers Squibb, Novartis and Pfizer. Please see the full study for all other authors’ relevant financial disclosures.
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