A phase 2 study incorporating sorafenib into the chemotherapy for older adults with FLT3-mutated acute myeloid leukemia: CALGB 11001

Geoffrey L Uy, Sumithra J Mandrekar, Kristina Laumann, Guido Marcucci, Weiqiang Zhao, Mark J Levis, Heidi D Klepin, Maria R Baer, Bayard L Powell, Peter Westervelt, Daniel J DeAngelo, Wendy Stock, Ben Sanford, William G Blum, Clara D Bloomfield, Richard M Stone, Richard A Larson, Geoffrey L Uy, Sumithra J Mandrekar, Kristina Laumann, Guido Marcucci, Weiqiang Zhao, Mark J Levis, Heidi D Klepin, Maria R Baer, Bayard L Powell, Peter Westervelt, Daniel J DeAngelo, Wendy Stock, Ben Sanford, William G Blum, Clara D Bloomfield, Richard M Stone, Richard A Larson

Abstract

The Cancer and Leukemia Group B (CALGB), now part of the Alliance for Clinical Trials in Oncology, conducted a multicenter, single-arm, phase 2 study in patients ≥60 years with FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML). In this study, sorafenib was added to daunorubicin and cytarabine-based induction and consolidation chemotherapy and was also continued for 12 months of maintenance therapy. The primary end point of the study was overall survival (OS) at 1 year in the FLT3 internal tandem duplication (FLT3-ITD) cohort. Fifty-four patients with a median age of 67 years (range, 60.3-82.7 years) were enrolled; 39 were FLT3-ITD patients (71%) and 15 were FLT3-TKD (29%) patients. The observed 1-year OS (95% confidence interval [CI]) was 62% (45%-78%) for the FLT3-ITD patients (meeting the primary end point 62% vs 30% for a historical control group, P < .0001) and 71% (42%-92%) for the FLT3-TKD patients. The median disease-free survival and OS were 12.2 months (95% CI, 5-16.9) and 15.0 months (95% CI, 10.4-20.1), respectively, in the FLT3-ITD group and 9.6 (95% CI, 1.9 to not available [NA]) and 16.2 months (95% CI, 5.0 to NA) for the FLT3-TKD group. This study suggests that the addition of sorafenib to chemotherapy for FLT3-ITD AML is feasible and may improve the survival of older adults with FLT3-mutated AML. This trial was registered at www.clinicaltrials.gov as #NCT01253070.

Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
FLT3 mutation screening. WT denotes wild-type alleles.
Figure 2.
Figure 2.
Overall outcomes of FLT3-mutated AML treated with sorafenib. Kaplan-Meier curves for OS (A), DFS (B), and EFS (C).
Figure 3.
Figure 3.
Kaplan-Meier curves for OS and EFS for FLT3-ITD patients by age. (A) Patients aged 60 to 69 years. (B) Patients aged ≥70 years.
Figure 4.
Figure 4.
Sensitivity analysis for effect of allo-HCT. Kaplan-Meier curves for OS (A) and EFS (B) with and without censoring for allo-HCT by FLT3-mutated subgroups.
Figure 5.
Figure 5.
FLT3 PIA. PIA was measured on day +6 of induction, cycle 1 day +15 of consolidation therapy, and cycle 1 day +15 of maintenance sorafenib. Results are expressed as percent change in FLT3 autophosphorylation from baseline. Bars plot median and interquartile range for subjects with FLT3-ITD or FLT3-TKD.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi