Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial

Röllig, Christoph; Serve, Hubert; Hüttmann, Andreas; Noppeney, Richard; Müller‐Tidow, Carsten; Krug, Utz; Baldus, Claudia D.; Brandts, Christian; Kunzmann, Volker; Einsele, Hermann; Krämer, Alwin; Schäfer‐Eckart, Kerstin; Neubauer, Andreas; Burchert, Andreas; Giagounidis, Aristoteles; Krause, Stefan W.; Mackensen, Andréas; Aulitzky, Walter E.; Herbst, Regina; Hänel, Mathias; Kiani, Alexander; Frickhofen, Norbert; Kullmer, Johannes; Kaiser, Ulrich; Link, Hartmut; Geer, Thomas; Reichle, A.; Junghanß, Christian; Repp, Roland; Heits, Frank; Dürk, Heinz; Hase, Jana; Klut, Ina-Maria; Illmer, Thomas; Bornhäuser, Martin; Schaich, Markus; Parmentier, Stefani; Görner, Martin; Thiede, Christian; Bonin, Malte von; Schetelig, Johannes; Kramer, Michael; Berdel, Wolfgang E.; Ehninger, Gerhard

doi:10.1016/s1470-2045(15)00362-9

Cited by 363 publications

(336 citation statements)

References 32 publications

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“…61 Randomized trials evaluating intensive chemotherapy with other FLT3 inhibitors, such as lestaurtinib and sorafenib, failed to show an improvement in response rate and in OS. [281][282][283][284] The trial with sorafenib in younger patients (not restricted to AML with FLT3 mutations) showed an improvement in EFS, mainly reflecting results in patients without FLT3-ITD, that did not translate into a significant OS benefit. 284 Randomized trials evaluating next-generation FLT3 inhibitors are ongoing.…”

Section: Novel Therapiesmentioning

confidence: 99%

Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel

Döhner

Estey

Grimwade

et al. 2017

Blood

4,685

5,387

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The first edition of the European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML) in adults, published in 2010, has found broad acceptance by physicians and investigators caring for patients with AML. Recent advances, for example, in the discovery of the genomic landscape of the disease, in the development of assays for genetic testing and for detecting minimal residual disease (MRD), as well as in the development of novel antileukemic agents, prompted an international panel to provide updated evidence- and expert opinion-based recommendations. The recommendations include a revised version of the ELN genetic categories, a proposal for a response category based on MRD status, and criteria for progressive disease

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Section: Novel Therapiesmentioning

confidence: 99%

Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel

Döhner

Estey

Grimwade

et al. 2017

Blood

4,685

5,387

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“…102,103 The addition of sorafenib to chemotherapy has also yielded positive data in a phase I and II study. 104,105 In the phase II study in younger adult (age range, 18-60 years) AML patients (n=267, the opposite was the case in a recently published trial. 107 Within this study, sorafenib was added to daunorubicin and cytarabine-based induction and consolidation chemotherapy and was also continued for 12 months of maintenance therapy.…”

Section: Results Of Clinical Trials With Tyrosine Kinase Inhibitor Trmentioning

confidence: 98%

Targeting the FLT3 Mutation in Acute Myeloid Leukaemia

Käyser¹,

Schlenk²

2017

European Oncology &Amp; Haematology

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A cute myeloid leukaemia (AML) exhibiting an internal tandem duplication of the FLT3 gene (FLT3-ITD) is an aggressive haematologic malignancy with a poor prognosis due to a high relapse rate and very limited options after relapse with conventional salvage regimens, whereas the prognostic impact of point mutations in the tyrosine kinase domain of the FLT3 gene (FLT3-TKD) are less clear. A number of tyrosine kinase inhibitors (TKIs) have been developed that inhibit the constitutively activated kinase activity caused by the FLT3 mutation, thus interrupting signalling pathways. Early clinical trials of these agents as monotherapy failed to elicit enduring complete responses, leading to clinical testing of FLT3 TKI in combination with conventional chemotherapy. Midostaurin has demonstrated improved survival in combination with standard intensive chemotherapy as compared to standard chemotherapy alone in younger adult patients with newly diagnosed FLT3-mutated AML and is the first and currently the only approved FLT3 TKI. Newer, more selective compounds, such as gilteritinib and crenolanib, have also demonstrated significant potency and specificity. Several combination trials are ongoing or planned in both relapsed and newly diagnosed AML patients with activating FLT3 mutations. KeywordsAcute myeloid leukaemia, FLT3 mutations, tyrosine kinase inhibitors, intensive chemotherapy, allogeneic stem cell transplantation Disclosure: Sabine Kayser is a member of the speakers'

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“…The addition of sorafenib was associated with a significant improvement in eventfree survival (3-year event-free survival rates 40% versus 22%; median EFS 21 versus 9 months; p 5 0.013). This improvement occurred in all patients with AML rather than only those with FLT3-ITD mutations [142]. This suggests that FLT3 inhibitors may also have anti-AML effects in FLT3 wild-type AML, or that sorafenib, a multikinase inhibitor, may exert anti-AML activity in mechanisms other than FLT3 inhibition.…”

Section: Flt3 Inhibitorsmentioning

confidence: 86%

Acute myeloid leukemia—Major progress over four decades and glimpses into the future

2015

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Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial

Cited by 363 publications

References 32 publications

Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel

Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel

Targeting the FLT3 Mutation in Acute Myeloid Leukaemia

Acute myeloid leukemia—Major progress over four decades and glimpses into the future

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