Table 2 Safety and efficacy profiles of the included studies for MBC

Ibrahim NK 2005 [24]

Phase II Multicenter

63

Mixed

300 mg/m² q3w

9

51

91

24

64

11

40

13

48

14.8

39

First

300 mg/m² q3w

64

24

Further

300 mg/m² q3w

21

Gradishar WJ 2005 [19]

Phase III RCT Multicenter

229

Mixed

260 mg/m² q3w

30

7

10

7

33

15.2

97

First

260 mg/m² q3w

42

132

Further

260 mg/m² q3w

27

13.2

Blum JL 2007 [6]

Phase II Multicenter

106

Further

100 mg/m² qw 3/4

49

18

62

19

25

8

37

5

14

26

3

9.2

75

Further

125 mg/m² qw 3/4

64

34

66

36

51

19

45

12

16

37

3.5

9.1

Guan ZZ 2009 [17]

Phase II RCT Multicenter

104

Further

260 mg/m² q3w

69

42

64

24

76

7

17

54

71

7.6

17.8

Mirtsching B 2011 [29]

Phase II Multicenter

72

First

125 mg/m² qw 3/4

14

11

11

1.4

54

8.3

58

6.9

42.2

68.8

14.5

29

Gradishar WJ 2009/2012 [15, 16]

Phase II RCT Multicenter

76

First

100 mg/m² qw 3/4

80

25

58

9

34

0

63

83

7.5

22.2

74

First

150 mg/m² qw 3/4

92

44

68

22

47

4

74

91

14.6

33.8

76

First

300 mg/m² q3w

93

44

73

21

36

5

46

72

10.9

27.7

Brezden B 2016 [4]

Phase II Multicenter

47

First

100 mg/m² qw 3/4

14.9

9

46.8

0

70

30

51

6

20.9

76

First

100 mg/m² qw 3/4

17.1

9

57.9

0

72

28

57

6.7

20

Ranade AA 2013 [36]

Phase II RCT Multicenter

55

Mixed

220 mg/m² q3w

28

1.5

40

67

53

Mixed

300 mg/m² q3w

38

17

40

72

Palumbo R 2015 [35]

Phase II Multicenter

52

Further

260 mg/m² q3w

77

21.2

88.5

25

48.1

5.8

27

0

48.1

76.9

8.9

Fabi A 2015 [14]

Phase II Single center

42

Further

Mixed

95

70

95

25

80

12

72

13

23.8

50

4.6

32

Further

125 mg/m² qw 3/4

28.1

50

10

Further

260 mg/m² q3w

10

50

Hurria A 2015 [21]

Phase II Multicenter

39

Mixed

100 mg/m² qw 3/4

26

3

36

5

8

0

31

5

31

69

5.7

19.4

Andres FT 2015 [1]

Phase II RCT Multicenter

21

Mixed

100 mg/m² qw 3/4

38

14

48

5

54

10

38

52

3.7

Jain MM 2016 [25]

Phase III RCT Multicenter

58

Mixed

260 mg/m² q3w

33

21

28

16

60

17

36

7

43

75

7.9

Yamamoto S 2017 [42]

Phase II Multicenter

35

Mixed

180 mg/m² q3w

46

0

23

51

6.5

44.7

Tamura K 2017 [39]

Phase II RCT Multicenter

98

First

150 mg/m² qw 3/4

97

78

96

58

88

22

33

1

61.2

96.9

11.2

42.4

Bernardo A 2017 [5]

Cohort

209

Further

Mixed

9.4

3

29.9

2.1

27.4

1.7

32.1

57.7

18

68

Further

125 mg/m² qw 3/4

8.7

1.1

17.4

2.2

12

1.1

31.5

54.3

16.9

121

Further

260 mg/m² q3w

9.9

4.2

38

2.1

37.3

2.1

32.4

59.9

18

Gennari A 2018 [18]

Phase II RCT Multicenter

83

First

150 mg/m² q2w

55.4

21.7

69.5

8

48.2

47

65.1

7.9

25.8

86

First

100 mg/m² qw 3/4

68.6

27.9

73.2

5.8

46.5

54.7

68.6

9

26.2

86

First

75 mg/m² qw

72.2

24.4

70

5.8

10.5

44.7

60.5

8.5

25.5

Marschner N 2018 [32]

Cohort Multicenter

697

Mixed

Mixed

4

7.5

39.6

4.3

20.8

1.3

37.2

68.3

5.9

15.6

491

Mixed

≤150 mg/m² qw

39.1

68.8

6

16.3

194

Mixed

220-260 mg/m² q3w

33

67.5

5.7

15.1

Hurria A 2019 [23]

Phase II Multicenter

40

Mixed

100 mg/m² qw 3/4

44

11

18

3

10

5

55

5

35

75

6.5

21.2

Ciruelos E 2019 [7]

Phase II RCT Multicenter

16

First

100 mg/m² qw 3/4

37.5

0

50.1

6.3

81.3

0

43.9

6.3

37.5

14

First

150 mg/m² q2w

18.8

0

25.1

6.3

62.6

0

87.6

0

12.5

16

First

150 mg/m² qw 3/4

64.2

50

50

28.6

78.6

35.7

64.3

14.3

42.9

Hara F 2019 [22]

Phase II RCT Multicenter

48

Mixed

180 mg/m² q3w

50

14.6

60.4

14.6

81.3

8.3

70.8

0

37.8

6.8

45

Mixed

220 mg/m² q3w

73.3

37.7

77.8

26.6

84.4

8.9

77.8

0

44.1

7.3

47

Mixed

260 mg/m² q3w

57.4

25.4

66

19.1

91.5

31.9

80.9

2.1

48.7

6.7

Schmid P 2020 [38]

Phase III RCT Multicenter

449

First

100 mg/m² qw 3/4

15

8.2

23

2.7

44

3

45.9

72.4

5.5

18.7