Table 1 Characteristics of included studies

Rollig C, 2015 [15]

SORAML; NCT00893373;

Phase 2, Germany

Aged 18–60 yrs, newly diagnosed de novo or secondary AML

(excluding APL)

Sorafenib 400 mg twice daily plus standard chemo—ind/cons/main up to 12 mths

N = 138^a

Placebo plus standard chemo

N = 138^a

Median age (range):

50 (43–46);

de novo AML: NR;

2° AML: 10%;

High-risk MDS: NR

Median age (range):

50 (44–55);

de novo AML: NR;

2° AML: 15%;

High-risk MDS: NR

1°: EFS

2°: RFS, OS, CR, tox

FU: 36 mths

Serve H, 2013 [16]

NCT00373373;

Phase 2, Germany

Aged > 60 yrs, de novo or secondary AML or AML from MDS

(excluding FAB type M3)

Sorafenib 400 mg twice daily plus intensive chemo—ind/cons

N = 104^a

Placebo plus intensive chemo

N = 97^a

Median age (range): 67.5 (61–78);

de novo AML: 60%;

2° AML: 40%;

High-risk MDS: NR

Median age (range):

69 (61–80);

de novo AML: 61%;

2° AML: 39%;

High-risk MDS: NR

1°: EFS

2°: OS, CR rate, tolerability

FU: 29.3 mths

Knapper S, 2017 [17]

AML15; ISRCTN17161961;

Phase 3, UK Denmark, NZ

Aged < 60 yrs, de novo or secondary AML, FLT3 mutation

(excluding APL)

Lestaurtinib 80 mg, twice daily after each of 4 courses of intensive chemo—ind/cons

N = 88

Intensive chemo

N = 87

Median age (range):

48 (16–66);

de novo AML: 95%;

2° AML: 3%;

High-risk MDS: 0%

Median age (range):

46 (16-65);

de novo AML: 97%;

2° AML: 5%;

High-risk MDS: 0%

1°: OS/RFS

2°: CR, CRi, OS, haem recovery times, tox, resource use

FU: 50.5 mths

Knapper S, 2017 [17]

AML17; ISRCTN55675535

Phase 3, UK Denmark, NZ

Aged < 60 yrs, de novo or secondary AML, FLT3 mutation

(excluding APL)

Lestaurtinib 80 mg, twice daily plus 1st line intensive chemo—ind/cons

N = 212

Placebo plus 1st line intensive chemo

N = 113

Median age (range):

50 (5–68);

de novo AML: 93%;

2° AML: 5%;

High-risk MDS: 2%

Median age (range):

50 (6–65);

de novo AML: 92%;

2° AML: 5%;

High-risk MDS: 3%

1°: OS/RFS

2°: CR, CRi, OS, haem recovery times, tox, resource use

FU: 50.5 mths

Levis M, 2011 [18]

Cephalon-204; NCT00079482;

Phase 2, Australia, Canada, EU, Israel, NZ, Russia, Ukraine, USA

Aged ≥ 18 yrs, AML with 1st relapse after 1st remission of 1–24 mths, FLT3 mutation

Salvage chemo followed by lestaurtinib 80 mg, twice daily

N = 112

Salvage chemo

N = 112

Median age (range):

59 (20–81);

de novo AML: NR;

2° AML: NR;

High-risk MDS: NR

Median age (range):

54 (21–79);

de novo AML: NR;

2° AML: NR;

High-risk MDS: NR

1°: CR, CRp

2°: OS, PR, tox, tolerability

FU: not reported

Stone RM, 2017 [19]

RATIFY calgb 10603; NCT00651261;

Phase 3, Canada, USA

Aged 18–59 yrs, newly diagnosed AML, FLT3 mutation

(excluding APL)

Midostaurin 50 mg twice daily plus standard chemo—ind/cons/main up to 12 mths

N = 360

Placebo 50 mg twice daily plus standard chemo

N = 357

Median age (range):

47.1 (19–60);

de novo AML: NR;

2° AML: NR;

High-risk MDS: NR

Median age (range):

48.6 (18–61);

de novo AML: NR;

2° AML: NR;

High-risk MDS: NR

1°: OS

2°: EFS, OS, CR rate, DFS, HCT rate

FU: 59 mths

Perl AE, 2019 [21]

ADMIRAL;

NCT02421939;

Phase 3, 14 countries

Aged > 18 yrs, relapsed or refractory AML, FLT3 mutation

Gilteritinib 120 mg, once daily in 28-day cycles

N = 247

Salvage chemo

N = 124

Median age (range):

62.0 (20.0–84.0);

de novo AML: NR;

2° AML: NR;

High-risk MDS: NR

Median age (range):

61.5 (19.0–85.0);

de novo AML: NR;

2° AML: NR;

High-risk MDS: NR

1°: OS, CR

2°: EFS, tox

FU: 17.8 mths

Cortes JE, 2019 [20]

QuANTUM-R; NCT02039726;

Phase 3, 19 countries

Aged > 18 yrs, relapsed or refractory AML, FLT3-ITD mutation

(excluding APL)

Quizartinib 20–60 mg as appropriate, once daily in continuous 28-day cycles

N = 245

Salvage chemo

N = 122

Median age (range):

55.0 (46.0–65.0);

de novo AML: NR;

2° AML: NR;

High-risk MDS: NR

Median age (range):

57.5 (44.0–66.0);

de novo AML: NR;

2° AML: NR;

High-risk MDS: NR

1°: OS

2°: EFS, CR, early death (30- and 60-day mortality)

FU: 23.5 mths