As reported in The Lancet by Erba et al, the phase III QuANTUM-First trial has shown prolonged overall survival with the addition of the FLT3 inhibitor quizartinib to chemotherapy in patients with newly diagnosed FLT3-internal-tandem-duplication (ITD)-positive acute myeloid leukemia (AML).
In the double-blind trial, 539 patients aged 18–75 years from sites in 26 countries were randomly assigned between September 2016 and August 2019 to receive quizartinib (n = 268) or placebo (n = 271) plus chemotherapy. Induction therapy consisted of cytarabine at 100 mg/m² per day via continuous infusion from day 1 to 7 and anthracycline (daunorubicin at 60 mg/m² per day or idarubicin at 12 mg/m² per day) on days 1, 2, and 3, then quizartinib at 40 mg or placebo once per day starting on day 8 for 14 days. Patients with complete remission or complete remission with incomplete neutrophil or platelet recovery received consolidation with high-dose cytarabine plus quizartinib at 40 mg per day or placebo, allogeneic hematopoietic cell transplantation (allo-HCT), or both, followed by continuation of single-agent quizartinib or placebo for up to 3 years. The primary endpoint was overall survival in the intent-to-treat population.
Median follow-up was 39.2 months (interquartile range = 31.9–45.8 months). A total of 173 patients in the quizartinib group and 175 in the control group proceeded to consolidation and 116 and 92 entered continuation. Median overall survival was 31.9 months (95% confidence interval [CI] = 21.0 months to not estimable) in the quizartinib group vs 15.1 months (95% CI = 13.2–26.2 months) in the control group (hazard ratio [HR] = 0.78, 95% CI = 0.62–0.98, P = .032). HRs favored quizartinib across most prespecified subgroups. In a post hoc subgroup analysis by age, the HRs were 0.68 (95% CI = 0.49–0.95) among patients aged < 60 years and 0.91 (95% CI = 0.66–1.26) among those aged ≥ 60 years. Event-free survival was not significantly prolonged in the quizartinib group (HR = 0.92 (95% CI = 0.75–1.11, P = .24).
Among 147 patients in the quizartinib group and 150 in the control group with complete remission during induction, median relapse-free survival was 39.3 months (95% CI = 22.6 months to not estimable) in the quizartinib group vs 13.6 months (95% CI = 9.7–23.7 months) in the control group (HR = 0.61, 95% CI = 0.44–0.85). Among these patients, the cumulative incidence of relapse at 12, 24, and 36 months was 19% vs 35%, 31% vs 43%, and 34% vs 45%.
Grade ≥ 3 adverse events occurred in 92% of the quizartinib group and 90% of the control group. The most common grade 3 or 4 adverse events were febrile neutropenia (43% vs 41%), hypokalemia (19% vs 16%), and pneumonia (11% vs 11%) in both groups and neutropenia (18% vs 9%) in the quizartinib group. Serious adverse events occurred in 56% vs 44% of patients, most commonly febrile neutropenia (11% vs 8%). Adverse events led to treatment discontinuation in 20% vs 9% of patients. Adverse events led to death in 11% vs 10% of patients, most commonly infection (8% vs 4%).
The investigators concluded: “The addition of quizartinib to standard chemotherapy with or without allo-HCT, followed by continuation monotherapy for up to 3 years, resulted in improved overall survival in adults aged 18–75 years with FLT3-ITD–positive newly diagnosed AML. Based on the results from the QuANTUM-First trial, quizartinib provides a new, effective, and generally well tolerated treatment option for adult patients with FLT3-ITD–positive newly diagnosed AML.”
Harry P. Erba, MD, Duke Cancer Institute, is the corresponding author for The Lancet article.
Disclosure: The study was funded by Daiichi Sankyo. For full disclosures of the study authors, visit www.thelancet.com.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.