In patients with acute myeloid leukemia (AML) positive for internal tandem duplication (ITD) mutations of FLT3, the selective type 2 FLT3 inhibitor quizartinib plus chemotherapy improved overall survival in adults aged 18–75 years, according to QuANTUM-First investigators. The regimen was administered with or without allogeneic hematopoietic cell transplantation (allo-HCT) and was followed by continuation monotherapy for up to 3 years.
At 193 hospitals and clinics in 26 countries in Europe, North America, Asia, Australia, and South America, 539 adult patients (294 [55%] male patients and 245 [45%] female patients) with FLT3-ITD-positive AML received induction therapy and were then randomized to quizartinib 40 mg orally or placebo once per day, starting on day 8, for 14 days. Those in complete remission or complete remission with incomplete neutrophil or platelet recovery received standard consolidation with high-dose cytarabine plus quizartinib 40 mg per day orally or placebo, allo-HCT, or both as consolidation therapy, followed by the continuation of single-agent quizartinib or placebo for up to 3 years.
Based on a primary outcome of overall survival, the investigators found: “148 (55%) of 268 patients in the quizartinib group and 168 (62%) of 271 patients in the placebo group discontinued the study, primarily because of death (133 [90%] of 148 in the quizartinib group vs 158 [94%] of 168 in the placebo group) or withdrawal of consent (13 [9%] of 148 in the quizartinib group vs 9 [5%] of 168 in the placebo group). Median age was 56 years (range 20–75, IQR 46.0–65.0). At a median follow-up of 39.2 months (IQR 31.9–45.8), median overall survival was 31.9 months (95% CI 21.0–not estimable) for quizartinib versus 15.1 months (13.2–26.2) for placebo (hazard ratio 0.78, 95% CI 0.62–0.98, P = 0.032). Similar proportions of patients in the quizartinib and placebo groups had at least one adverse event (264 [100%] of 265 in the quizartinib group and 265 [99%] of 268 in the placebo group) and one grade 3 or higher adverse event (244 [92%] of 265 in the quizartinib group and 240 [90%] of 268 in the placebo group). The most common grade 3 or 4 adverse events were febrile neutropenia, hypokalaemia, and pneumonia in both groups and neutropenia in the quizartinib group.”