Sorafenib maintenance therapy reduces risk for relapse, death in AML subset
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Sorafenib maintenance therapy reduced the risk for relapse and death after hematopoietic stem cell transplantation among a subset of patients with acute myeloid leukemia, according to study results published in Journal of Clinical Oncology.
Researchers observed the benefit in the randomized phase 2 SORMAIN trial among patients with FLT3 internal tandem duplication (FLT3-ITD) mutations.
“Prognosis with AML varies substantially depending on cytogenetics, mutation status, age and comorbidities,” Andreas Burchert, MD, clinical researcher at Philipps University of Marburg in Germany, and colleagues wrote. “Because FLT3-ITD causes oncogenic addiction, it emerged as a bona de target for therapeutic intervention in FLT3-ITD-positive AML.”
Front-line therapy with a combination of chemotherapy and midostaurin (Rydapt, Novartis), a multitargeted tyrosine kinase inhibitor, has been shown to improve OS for patients with FLT3-ITD-mutated AML. Treatment with other more specific and potent FLT3 inhibitors, such as quizartinib (AC220, Daiichi Sankyo) or gilteritinib (Xospata, Astellas Pharma), has improved OS for patients with relapsed or refractory FLT3-mutated AML, according to study background.
However, it remained unknown whether maintenance therapy with FLT3 inhibitors, such as sorafenib (Nexavar, Bayer), improved patient outcomes after HSCT.
For that reason, Burchert and colleagues randomly assigned 83 patients (median age, 54 years; range, 18-75; 50.6% women) with FLT3-ITD-positive AML who were in complete hematologic remission after HSCT to sorafenib (n = 43) or placebo (n = 40) for 24 months.
RFS served as the primary endpoint. Researchers defined relapse as disease relapse or death, whichever occurred first.
Median follow-up was 41.8 months.
Results showed superior 24-month RFS probability among patients in the sorafenib group vs. the placebo group (85% vs. 53.3%; HR = 0.25; 95% CI, 0.1-0.65). Median RFS was not reached with sorafenib vs. 30.9 months with placebo.
HR for relapse or death among patients who received sorafenib vs. placebo was 0.39 (95% CI, 0.18-0.85).
Exploratory data showed patients with undetectable minimal residual disease before HSCT and those with detectable minimal residual disease after HSCT benefited most from sorafenib. Additionally, sorafenib maintenance treatment did not significantly increase toxicity compared with placebo.
“SORMAIN establishes targeted maintenance therapy as a novel efficacious treatment paradigm with the potential to meaningfully improve outcome after [HSCT],” Burchert and colleagues wrote. “Ongoing post-[HSCT] maintenance therapy studies use more FLT3-specic TKIs, such as quizartinib or gilteritinib. They could help to better understand to which extent FLT3 selectivity [vs.] immune-stimulatory off-target activities govern the overall efficacy of sorafenib.”
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