Table 2 Response by radiological criteria for patients in arm 1

From: The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial

Response

RANO-HGG

RAPNOc

RANO-LGG

n

n

n

ORR,a n (%)

69

46 (67)

76

39 (51)

76

40 (53)

 BRAF fusion

59

41 (69)

64

33 (52)

64

33 (52)

 BRAF mutation

10

5 (50)

12

6 (50)

12

7 (58)

 Prior MAPKi

41

29 (71)

45

22 (49)

45

23 (51)

 MAPKi-naive

28

17 (61)

31

17 (55)

31

17 (55)

CBR,a n (%) (SD of any length of time)

69

64 (93)

76

62 (82)

76

63 (83)

 BRAF fusion

59

55 (93)

64

53 (83)

64

53 (83)

 BRAF mutation

10

9 (90)

12

9 (75)

12

10 (83)

 Prior MAPKi

41

37 (90)

45

38 (84)

45

38 (84)

 MAPKi-naive

28

27 (96)

31

24 (77)

31

25 (81)

CBR,a n (%) (SD ≥ 6 months)

69

57 (83)

76

45 (59)

76

52 (68)

 BRAF fusion

59

52 (88)

64

39 (61)

64

43 (67)

 BRAF mutation

10

5 (50)

12

6 (50)

12

9 (75)

 Prior MAPKi

41

34 (83)

45

26 (58)

45

31 (69)

 MAPKi-naive

28

23 (82)

31

19 (61)

31

21 (68)

CBR,a (SD ≥ 12 months)

69

54 (78)

76

43 (57)

76

46 (61)

 BRAF fusion

59

49 (83)

64

37 (58)

64

39 (61)

 BRAF mutation

10

5 (50)

12

6 (50)

12

7 (58)

 Prior MAPKi

41

33 (80)

45

25 (56)

45

26 (58)

 MAPKi-naive

28

21 (75)

31

18 (58)

31

20 (65)

BOR,a n (%)

69

 

76

 

76

 

CR

 

12 (17)

 

0

 

0

PR

 

34 (49)

 

28 (37)

 

20 (26)

MR

 

n/a

 

11 (14)

 

20 (26)

SD

 

18 (26)

 

23 (30)

 

23 (30)

 SD <12 months

 

10 (14)

 

19 (25)

 

17 (22)

 SD ≥12 months

 

8 (12)

 

4 (5)

 

6 (8)

PD

 

4 (6)

 

13 (17)

 

11 (14)

NE

 

1 (1)

 

1 (1)

 

2 (3)

Median DOR, months (95% CI)b

46

16.6 (11.6–NR)

39

13.8 (11.3–NR)

40

14.4 (11.0–NR)

 BRAF fusion

41

16.8 (11.6–NR)

33

13.8 (11.3–NR)

33

16.3 (11.0–NR)

 BRAF mutation

5

15.1 (8.3–NR)

6

NR (8.4–NR)

7

12.0 (8.4–NR)

 Prior MAPKi

29

15.1 (9.0–16.8)

22

13.8 (11.3–NR)

23

12.0 (8.5–NR)

 MAPKi-naive

17

NR (11.6–NR)

17

NR (8.4–NR)

17

16.3 (8.4–NR)

Median TTR, months (range)

46

3.0 (2.6–16.6)

39

5.3 (1.6–11.2)

40

5.5 (1.6–11.3)

 BRAF fusion

41

3.0 (2.6–16.6)

33

5.5 (2.3–11.2)

33

5.5 (2.3–11.0)

 BRAF mutation

5

2.7 (2.6–16.4)

6

2.8 (1.6–3.0)

7

2.9 (1.6–11.3)

 Prior MAPKi

29

2.8 (2.6–16.6)

22

5.4 (1.6–11.2)

23

5.5 (1.6–11.3)

 MAPKi-naive

17

5.3 (2.6–11.1)

17

5.3 (2.3–11.0)

17

5.3 (2.3–11.0)

  1. aORR, CBR and BOR for RAPNO and RANO-LGG criteria included MRs (that is, ORR = CR + PR + MR; CBR = CR + PR + MR + SD (calculated based on SD of any length of time, SD ≥ 6 months and SD ≥ 12 months)). For CR, PR and MR, confirmation of response by a subsequent scan approximately 3 months after the initial response was required.
  2. bThe 95% CIs were calculated using the Kaplan–Meier method.
  3. cA subgroup analysis of IRC-assessed ORR based on RAPNO criteria (sex, age group, race, geographical location (US/ex-US)) was conducted. Although the small number of patients in some subgroups limits interpretation of these data, responses were observed among all subgroups, with no trends in ORR apparent (Extended Data Fig. 3). Patients with BRAF duplication or rearrangement are considered in the BRAF fusion group. n/a, not applicable.
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