Table 3.
Characteristics of diarrhoea under neratinib therapy in the ExteNET and CONTROL studies (safety population; datacut for dose escalation cohort: Oct 19, 2020, datacut for all other CONTROL study cohorts: Oct 21, 2019) [53, 54]
| CONTROL |
ExteNET |
|||||
|---|---|---|---|---|---|---|
| n = 137 | n = 64 | n = 136 | n = 104 | n = 60 | n = 1,408 | |
| Neratinib dose | Neratinib | Neratinib | Neratinib | Neratinib | Neratinib dose | Neratinib |
| 240 mg/d | 240 mg/d | 240 mg/d | 240 mg/d | escalationc | 240 mg/d | |
|
| ||||||
| Loperamide prophylaxis | Loperamidea | Loperamidea | Loperamideb | No primary | ||
| first 8 weeks | first 8 weeks | first 4 weeks | prophylaxis | |||
|
| ||||||
| Other diarrhea prophylaxis | Budesonide | Colestipol | Colestipol | |||
| 9 mg/d for | 2g bid for | 2g bid for | ||||
| 1 cycle | 1 cycle | 1 cycle | ||||
|
| ||||||
| Treatment-emergent diarrhoea incidence, n (%) | ||||||
| No diarrhoea | 28 (20) | 9 (14) | 23 (17) | 5 (5) | 1 (1.7) | 65 (5) |
| Grade 1 | 33 (24) | 16 (25) | 38 (28) | 34 (33) | 24 (40) | 323 (23) |
| Grade 2 | 34 (25) | 21 (33) | 47 (35) | 32 (31) | 27 (45) | 458 (33) |
| Grade 3 | 42 (31) | 18 (28) | 28 (21) | 33 (32) | 8 (13.3) | 561 (40) |
| Grade 4 | 0 | 0 | 0 | 0 | 0 | 1 (<1) |
|
| ||||||
| Characteristics of grade ≥ 3 diarrhoea | ||||||
| Median episodes/patient (IQR) | 1 (1–2) | 1 (1–2) | 1 (1–2) | 1 (1–3) | 2 (n.r.) | 2 (1–3) |
| Median duration of episode, days (IQR) | 2 (1–3) | 1 (1–2) | 1 (1–2) | 1 (1–2) | n.r. | 2 (1–3) |
| Median time to first episode, days (IQR) | 7 (5–13) | 19 (7–45) | 41 (7–189) | 15 (8–47) | 45 (n.r.) | 8 (4–33) |
| Median cumulative durationd, days (IQR) | 3 (2–6) | 3 (1–3) | 4 (1–6) | 2 (1–6) | 2.5 (n.r.) | 5 (2–9) |
|
| ||||||
| Action taken, n (%) | ||||||
| Dose hold | 20 (15) | 12 (19) | 22 (16) | 15 (14) | 7 (11.7) | 477 (34) |
| Dose reduction | 10 (7) | 3 (5) | 10 (7) | 12 (12) | 2 (3.3) | 372 (26) |
| Discontinuation | 28 (20) | 5 (8) | 5 (4) | 8 (8) | 2 (3.3) | 237 (17) |
| Hospitalization | 2 (1) | 0 | 0 | 0 | 0 | 20 (1) |
a
4 mg initial; days 1–14: 4 mg tid; days 15–56: 4 mg bid;
b
4 mg initial; days 1–14: 4 mg tid; days 15–28: 4 mg bid;
c
dose escalation regimen #1: days 1–7: 120 mg/d; days 8–14: 160 mg/d, then 240 mg/d; dose escalation regimen #2 (days 1–14: 160 mg/d; days 15–28: 200 mg/d, then 240 mg/d) is not reported here;
d
defined as the sum of the durations of all episodes at that grade. Unless otherwise mandated, all patients received loperamide as needed (16 mg/d maximum) on days 1 − 364. IQR, interquartile range; n.r., not reported.