Patient demographics, baseline characteristics, prior treatments, disposition, and dabrafenib exposurea
| Part 1 | Part 2 | |||||
|---|---|---|---|---|---|---|
| Characteristic | Dabrafenib 3.75 mg/kg (n = 3) | Dabrafenib 4.5 mg/kg (n = 6) | Dabrafenib 5.25 mg/kg (n = 6) | Dabrafenib RP2D (n = 17) | All patients treated with dabrafenib at RP2D (n = 24) | All patients with LGG (N = 32) |
| Median age (range), years | 8 (4–13) | 8.5 (2–16) | 7.5 (3–11) | 11 (2–17) | 9.5 (2–17) | 8.5 (2–17) |
| <2 years, n | 0 | 0 | 0 | 0 | 0 | 0 |
| 2–<6 years, n | 1 | 2 | 2 | 5 | 7 | 10 |
| 6–<12 years, n | 1 | 3 | 4 | 4 | 8 | 12 |
| 12–≤18 years, n | 1 | 1 | 0 | 8 | 9 | 10 |
| Sex, n (%) | ||||||
| Male | 2 (67) | 5 (83) | 3 (50) | 9 (53) | 13 (54) | 19 (59) |
| Female | 1 (33) | 1 (17) | 3 (50) | 8 (47) | 11 (46) | 13 (41) |
| Race, n (%) | ||||||
| White | 3 (100) | 5 (83) | 6 (100) | 13 (76) | 19 (79) | 27 (84) |
| Black | 0 | 1 (17) | 0 | 2 (12) | 3 (13) | 3 (9) |
| Asian | 0 | 0 | 0 | 2 (12) | 2 (8) | 2 (6) |
| Performance status, n (%)b | ||||||
| 100 | 2 (67) | 3 (50) | 3 (50) | 9 (53) | 12 (50) | 17 (53) |
| 80–90 | 1 (33) | 1 (17) | 2 (33) | 7 (41) | 10 (42) | 11 (34) |
| <80 | 0 | 2 (33) | 1 (17) | 1 (6) | 2 (8) | 4 (13) |
| Histology at initial diagnosis, n (%) | ||||||
| Pilocytic astrocytoma | 1 (33) | 3 (50) | 1 (17) | 8 (47) | 10 (42) | 13 (41) |
| Ganglioglioma | 0 | 1 (17) | 1 (17) | 5 (29) | 6 (25) | 7 (22) |
| Pleomorphic xanthoastrocytoma | 0 | 0 | 1 (17) | 2 (12) | 3 (13) | 3 (9) |
| Pilomyxoid astrocytoma | 1 (33) | 0 | 0 | 1 (6) | 1 (4) | 2 (6) |
| Otherc | 1 (33) | 2 (33) | 3 (50) | 1 (6) | 4 (17) | 7 (22) |
| Histologic grade at initial diagnosis, n (%)d | ||||||
| Grade I | 2 (67) | 4 (67) | 4 (67) | 12 (71) | 16 (67) | 22 (69) |
| Grade II | 1 (33) | 2 (33) | 2 (33) | 4 (24) | 7 (29) | 9 (28) |
| Median time since initial diagnosis (range), months | 36 (32–39) | 15 (11–90) | 39 (18–83) | 26 (6–190) | 31 (6–190) | 32 (6–190) |
| Prior treatments, n (%)e | ||||||
| Chemotherapy | 3 (100) | 5 (83) | 6 (100) | 14 (82) | 20 (83) | 28 (88) |
| Radiotherapy | 1 (33) | 1 (17) | 1 (17) | 3 (18) | 5 (21) | 6 (19) |
| Small-molecule therapy | 0 | 0 | 1 (17) | 1 (6) | 2 (8) | 2 (6) |
| Immunotherapy | 0 | 0 | 0 | 1 (6) | 1 (4) | 1 (3) |
| Other | 0 | 0 | 0 | 3 (18) | 3 (13) | 3 (9) |
| Median time from last recurrence to dabrafenib start (range), monthsf | NA | NA | 0.8 (0.2–1.3) | 1.1 (0.1–81.5) | 1.1 (0.1–81.5) | 1.1 (0.1–81.5) |
| Median time from last progression to dabrafenib start (range), monthsg | 7.6 (0.5–14.7) | 0.8 (0.5–1.1) | 1.8 (0.2–26.2) | 1.6 (0.1–10.3) | 1.5 (0.1–26.2) | 1.1 (0.1–26.2) |
| Continuing treatment, n (%) | 2 (67) | 3 (50) | 2 (33) | 8 (47) | 10 (42) | 15 (47) |
| Discontinued treatment, n (%) | 1 (33) | 3 (50) | 4 (67) | 9 (53) | 14 (58) | 17 (53) |
| Reasons for discontinuation | ||||||
| Investigator discretion | 1 (33) | 1 (17) | 4 (67) | 5 (29) | 10 (42) | 11 (34) |
| Disease progression | 0 | 2 (33) | 0 | 2 (12) | 2 (8) | 4 (13) |
| Adverse event | 0 | 0 | 0 | 2 (12) | 2 (8) | 2 (6) |
| Median duration of exposure to dabrafenib (range), weeks | 157 (62–159) | 120 (8–185) | 96 (25–152) | 105 (<1–149) | 104 (<1–152) | 108 (<1–185) |
| Patients with dose reductions and/or interruptions, n (%) | 1 (33) | 3 (50) | 1 (17) | 5 (29) | 6 (25) | 10 (31) |
Abbreviation: NA, not applicable.
↵aAs of data cutoff (September 12, 2017).
↵bUsing Karnofsky (≥16 years of age; n = 28) or Lansky (<16 years of age; n = 4) performance status, as appropriate.
↵cDesmoplastic neuroepithelial neoplasm, cervicomedullary tumor, glioneuronal brain stem tumor, posterior fossa brain tumor, optic pathway glioma, gliomatosis cerebri, and other low-grade glioma.
↵dOne patient had missing data for disease grade at initial diagnosis but was confirmed to have LGG.
↵ePatients may have had multiple therapies and prior therapy type was undetermined in 2 patients; best response to last therapy received included 5 patients with a partial response, 13 patients with stable disease, and 9 patients with progressive disease (response to last therapy was undetermined in 5 patients).
↵fIn 11 patients with recurrence.
↵gIn 25 patients with disease progression.