Sorafenib Demonstrates Survival Benefit in AML, More Safety Data Needed

The FMS-like tyrosine kinase 3 (FLT3) inhibitor sorafenib led to significantly improved survival compared with placebo in patients with acute myeloid leukemia (AML), according to a meta-analysis presented at the Society of Hematologic Oncology 2024 Annual Meeting.

“Mutations in the FLT3 gene occur in around one-third of AML patients. These mutations are associated with a worse prognosis,” the authors explained. “The FLT3 gene plays a crucial role in the growth and survival of cancer cells. FLT3 inhibitors have emerged as a promising treatment option to inhibit the aberrant signaling pathways driven by FLT3 mutations.”

The investigators collected data from randomized, controlled trials of FLT3 inhibitors—sorafenib, gilteritinib, and midostaurin—through April 2024. They searched Scopus, Web of Science, Cochrane Library, and PubMed, pooling data from 19 trials. The final analysis included a total of 2,975 patients.

Pooled data showed that sorafenib led to a superior overall survival rate compared with placebo (risk ratio [RR], 2.26; 95% CI, 1.33–3.84; P=0.003). However, there was no benefit found for sorafenib versus placebo in terms of hematological and gastrointestinal side effects.

The authors noted that gilteritinib showed a benefit versus placebo for hematological and gastrointestinal side effects, but it was not statistically significant (hematological side effects RR, 1.54, P=0.07; gastrointestinal side effects RR, 2.97, P=0.2).

“Our meta-analysis revealed a statistically significant improvement in overall survival with sorafenib compared to placebo. 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,” the authors concluded. They called for additional research 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 2,975 patients. Abstract #AML-611. Society of Hematologic Oncology 2024 Annual Meeting; Sept. 4-7, 2024; Houston, Texas.