Conference Coverage

Meta-Analysis: FLT3 Inhibitors vs Placebo for Patients With Acute Myeloid Leukemia

Anthony Calabro, MA

A meta-analysis of 19 randomized controlled trials (RCTs) showed a statistically significant improvement in overall survival with sorafenib when compared with placebo for patients with acute myeloid leukemia (AML). The study authors cautioned that, despite these results, more understanding of sorafenib’s safety profile was still needed. The authors’ findings were presented at the 12th annual meeting of the Society of Hematologic Oncology (SOHO 2024) in Houston, TX.

Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene occur in approximately one-third of patients with AML, according to the authors of the current study. The FLT3 gene plays a crucial role in the growth and survival of cancer cells, which can lead to a worse prognosis for this patient population. Fortunately, FLT3 inhibitors that curb the signaling pathways driven by FLT3 mutations are emerging as a treatment option for patients with AML.

Khaity and colleagues performed a meta-analysis that pooled data from 19 RCTs, totaling 2975 patients with AML, that individually compared FLT3 inhibitors, sorafenib, gilteritinib, and midostaurin with placebo. They searched Scopus, Web of Science, Cochrane Library, and PubMed for relevant RCTs from inception until April 2024, and screened patient data for eligible studies. All relevant outcomes were pooled as risk ratio (RR) in a random-effect model meta-analysis, the authors noted.

After pooling the patient data, Khaity and colleagues found that, when looking at overall survival, sorafenib was superior to placebo (RR = 2.26, 95% CI [1.33 to 3.84], P = 0.003). However, the hematological and gastrointestinal side effects were similar for both the sorafenib group (RR = 1.29, 95% CI [0.77 to 2.18], P = 0.3) and the placebo group (RR = 1.40, 95% CI [0.92 to 2.14], P = 0.1). Regarding the hematological and gastrointestinal side effects for gilteritinib versus placebo and midostaurin versus placebo, no significant differences were found.

“Our meta-analysis revealed a statistically significant improvement in overall survival with sorafenib compared to placebo,” the authors concluded. “However, while our findings suggest that sorafenib may offer a survival benefit, a more comprehensive understanding of its safety profile, alongside those of gilteritinib and midostaurin, is necessary. Further research is crucial to optimize treatment strategies and establish definitive guidelines for using FLT3 inhibitors in patients with AML.”

Reference:
Khaity A, Hussein AM, Al-dardery NM, et al. Safety and efficacy of flt3 inhibitors in acute myeloid leukemia: an updated meta-analysis of 2975 patients. In: Proceedings of the Society of Hematologic Oncology 2024 Annual Meeting. Clin Lymphoma Myeloma Leuk. 2024 Sept;9(24);Supplement 1:S302.