Please use this identifier to cite or link to this item: https://hdl.handle.net/1/2521
Title: Sorafenib plus intensive chemotherapy in newly diagnosed FLT3-ITD AML: a randomized, placebo-controlled study by the ALLG
Authors: Loo, Sun;Roberts, Andrew W;Anstee, Natasha S;Kennedy, Glen A;He, Simon;Schwarer, Anthony P;Enjeti, Anoop K;D'Rozario, James;Marlton, Paula;Bilmon, Ian A;Taper, John;Cull, Gavin;Tiley, Campbell ;Verner, Emma;Hahn, Uwe;Hiwase, Devendra K;Iland, Harry J;Murphy, Nick;Ramanathan, Sundra;Reynolds, John;Ong, Doen Ming;Tiong, Ing Soo;Wall, Meaghan;Murray, Michael;Rawling, Tristan;Leadbetter, Joanna;Rowley, Leesa;Latimer, Maya;Yuen, Sam;Ting, Stephen B;Fong, Chun Yew;Morris, Kirk;Bajel, Ashish;Seymour, John F;Levis, Mark J;Wei, Andrew H
Affliation: Central Coast Local Health District
Gosford Hospital
Issue Date: 7-Dec-2023
Source: 142(23):1960-1971
Journal title: Blood
Department: Haematology
Abstract: Sorafenib maintenance improves outcomes after hematopoietic cell transplant (HCT) for patients with FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) acute myeloid leukemia (AML). Although promising outcomes have been reported for sorafenib plus intensive chemotherapy, randomized data are limited. This placebo-controlled, phase 2 study (ACTRN12611001112954) randomized 102 patients (aged 18-65 years) 2:1 to sorafenib vs placebo (days 4-10) combined with intensive induction: idarubicin 12 mg/m2 on days 1 to 3 plus either cytarabine 1.5 g/m2 twice daily on days 1, 3, 5, and 7 (18-55 years) or 100 mg/m2 on days 1 to 7 (56-65 years), followed by consolidation and maintenance therapy for 12 months (post-HCT excluded) in newly diagnosed patients with FLT3-ITD AML. Four patients were excluded in a modified intention-to-treat final analysis (3 not commencing therapy and 1 was FLT3-ITD negative). Rates of complete remission (CR)/CR with incomplete hematologic recovery were high in both arms (sorafenib, 78%/9%; placebo, 70%/24%). With 49.1-months median follow-up, the primary end point of event-free survival (EFS) was not improved by sorafenib (2-year EFS 47.9% vs 45.4%; hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.51-1.51; P = .61). Two-year overall survival (OS) was 67% in the sorafenib arm and 58% in the placebo arm (HR, 0.76; 95% CI, 0.42-1.39). For patients who received HCT in first remission, theĀ 2-year OS rates were 84% and 67% in the sorafenib and placebo arms, respectively (HR, 0.45; 95% CI, 0.18-1.12; P = .08). In exploratory analyses, FLT3-ITD measurable residual disease (MRD) negative status (<0.001%) after induction was associated with improved 2-year OS (83% vs 60%; HR, 0.4; 95% CI, 0.17-0.93; P = .028). In conclusion, routine use of pretransplant sorafenib plus chemotherapy in unselected patients with FLT3-ITD AML is not supported by this study.
URI: https://hdl.handle.net/1/2521
DOI: 10.1182/blood.2023020301
Pubmed: https://pubmed.ncbi.nlm.nih.gov/37647654
Publicaton type: Journal Article
Keywords: Cancer
Study or Trial: Randomized Controlled Clinical Trial/Controlled Clinical Trial
Appears in Collections:Oncology / Cancer

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