EHA 2018: Single-Agent Quizartinib vs Chemotherapy in Relapsed or Refractory AML
Results from the phase III QuANTUM-R study of single-agent quizartinib in relapsed or refractory acute myeloid leukemia (AML) were presented by Cortes et al at the 23rd Annual Congress of the European Hematology Association (EHA) (Abstract LB2600).
Study Findings
QuANTUM-R study results showed that patients with relapsed/refractory AML with FLT3-ITD mutations who received single-agent quizartinib had a 24% reduction in the risk of death compared to patients who received salvage chemotherapy (hazard ratio [HR] = 0.76, 95% confidence interval [CI] = 0.58–0.98; P = .0177). The median overall survival was 6.2 months (two-sided 95% CI = 5.3–7.2 months) for patients treated with quizartinib and 4.7 months (two-sided 95% CI = 4.0–5.5 months) for patients treated with salvage chemotherapy. The estimated survival probability at 1 year was 27% for patients who received quizartinib and 20% for patients who received salvage chemotherapy.
“FLT3-ITD–mutated AML represents a high unmet need entity, as patients with this aggressive form of the disease have an overall dismal prognosis as evidenced by low response rates to current available therapies, high risk of relapse, and a shorter overall survival than those without this mutation,” said Jorge E. Cortes, MD, Deputy Chair of the Department of Leukemia in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. “In relapsed/refractory AML with FLT3-ITD mutations, these findings represent the first reported clinical data demonstrating that a single agent can significantly improve overall survival, suggesting that quizartinib could potentially help these patients live longer. Additionally, in the study, a higher proportion of patients received a stem cell transplant in the quizartinib arm compared to the chemotherapy arm.”
Secondary and key exploratory analyses including composite complete remission are consistent and supportive of the primary analysis.
Adverse Events
The safety profile observed in QuANTUM-R appears consistent with that observed at similar doses in the quizartinib clinical development program. The median treatment duration with quizartinib was 4 cycles of 28 days (97 days; range = 1–1,182 days) vs 1 cycle (range = 1–2 cycles) in the salvage chemotherapy arm. The median relative dose intensity for quizartinib was 89%.
The incidence of treatment-emergent adverse events was comparable between patients who received single-agent quizartinib (n = 241) and those who received salvage chemotherapy (n = 94). The most common adverse events (> 30%, any grade) in patients treated with quizartinib vs chemotherapy, respectively, included nausea (48% vs 42%), thrombocytopenia (39% vs 34%), fatigue (39% vs 29%), musculoskeletal pain (37% vs 28%), pyrexia (38% vs 45%), anemia (37% vs 32%), neutropenia (34% vs 26%), febrile neutropenia (34% vs 28%), vomiting (33% vs 21%), and hypokalemia (32% vs 28%).
The most common adverse events of grade ≥ 3 (> 10% of patients) were thrombocytopenia (35% vs 34%), anemia (30% vs 29%), neutropenia (32% vs 25%), febrile neutropenia (31% vs 21%), leukopenia (17% vs 16%), sepsis/septic shock (16% vs 18%), hypokalemia (12% vs 9%), and pneumonia (12% vs 9%). A corrected QT interval by Fredericia’s formula (QTcF) > 500 msec occurred in 8 patients (3.3%), and 2 out of 241 patients discontinued quizartinib due to QTcF prolongation. There were no reported events of grade 4 QTcF prolongation (torsades de pointes, sudden death, or cardiac arrest) in the quizartinib arm.
More About QuANTUM-R
QuANTUM-R is a global, phase III, open-label randomized study that enrolled 367 patients with FLT3-ITD–mutated AML who were refractory to or in relapse following (with duration of remission ≤ 6 months) standard first-line AML therapy with or without hematopoietic stem cell transplantation. Patients were randomly assigned in a 2:1 ratio to receive either single-agent oral quizartinib (60 mg, with 30-mg lead-in) or salvage chemotherapy. The primary objective of the study was to determine whether single-agent quizartinib prolonged overall survival compared to salvage chemotherapy.
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