Phase II trial of dose-escalated sorafenib in advanced solid tumors.

Semrad, Thomas J.; Eddings, Courtney; Pan, Chong Xian; Lau, David K.; Gandara, David R.; Beckett, Laurel A.; Lara, Primo

doi:10.1200/jco.2010.28.15_suppl.3055

Cited by 1 publication

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“…EFS was reported in three articles for two inhibitors, gilteritinib and quizartinib, and the mEFS was 2.703 months (95% CI 1.518, 3.889) (Figure 3D). Simultaneously, duration of therapy was reported in sorafenib, gilteritinib and quizartinib with the range of 1.94-4.6 months (Awada et al, 2005;Borthakur et al, 2011;Semrad et al, 2012;Chen et al, 2014;Lin et al, 2017;Perl et al, 2017;Cortes J. et al, 2018;Cortes JE. et al, 2018;Usuki et al, 2018;Cortes et al, 2019;Perl et al, 2019;Usuki et al, 2019;Burchert et al, 2020;Li et al, 2020;Fierro-Maya et al, 2021;Hosono et al, 2021;Huh et al, 2021;Numan et al, 2022;Dumas et al, 2023;Kudo et al, 2023).…”

Section: Efficacy Survival Outcomementioning

confidence: 97%

Efficacy and safety of FLT3 inhibitors in monotherapy of hematological and solid malignancies: a systemic analysis of clinical trials

Zhao,

Zhang,

Ding

et al. 2024

Front. Pharmacol.

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Introduction: FLT3 mutations are closely associated with the occurrence of hematological and solid malignancies, especially with acute myeloid leukemia. Currently, several FLT3 inhibitors are in clinical trials, and some have been applied in clinic. However, the safety, efficacy and pharmacodynamics of these FLT3 inhibitors have not been systemically analyzed before.Methods: We searched and reviewed clinical trial reports on the monotherapy of 13 FLT3 inhibitors, including sorafenib, lestaurtinib, midostaurin, gilteritinib, quizartinib, sunitinib, crenolanib, tandutinib, cabozantinib, pexidartinib, pacritinib, famitinib, and TAK-659 in patients with hematological and solid malignancies before May 31, 2023.Results: Our results showed the most common adverse events (AEs) were gastrointestinal adverse reactions, including diarrhea, hand-foot syndrome and nausea, while the most common hematological AEs were febrile neutropenia, anemia, and thrombocytopenia. Based on the published data, the mean overall survival (OS) and the mean progression-free survival (PFS) were 9.639 and 5.905 months, respectively. The incidence of overall response rate (ORR), complete remission (CR), partial response (PR), and stable disease (SD) for all these FLT3 inhibitors was 29.0%, 8.7%, 16.0%, and 42.3%, respectively. The ORRs of FLT3 inhibitors in hematologic malignancies and solid tumors were 40.8% and 18.8%, respectively, indicating FLT3 inhibitors were more effective for hematologic malignancies than for solid tumors. In addition, time to maximum plasma concentration (Tmax) in these FLT3 inhibitors ranged from 0.7-12.0 hours, but the elimination half-life (T1/2) range was highly variable, from 6.8 to 151.8 h.Discussion: FLT3 inhibitors monotherapy has shown significant anti-tumor effect in clinic, and the effectiveness may be further improved through combination medication.

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