Table 2.
Summary of safety in Cohorts I and II (evaluable population)
| Cohort I |
Cohort II | ||
|---|---|---|---|
| Placebo (n = 58) | Doxycycline (n = 56) | Alclometasone + probiotic (n = 59) | |
| Median relative dose intensitya (RDI) of dacomitinib in the first 8 weeks, % (range) | 78.87 (12.5–100) | 82.74 (12.5–100) | 75.00 (8.9–100) |
| Treatment-emergent adverse events (all causalities) in the first 8 weeks of treatment | |||
| Patients with adverse events, n (%) | 58 (100) | 56 (100) | 58 (98.3) |
| Patients with serious adverse events, n (%) | 12 (20.7) | 13 (23.2) | 11 (18.6) |
| Patients with grade 3 or 4 adverse events, n (%) | 25 (43.1) | 18 (32.1) | 29 (49.2) |
| Patients with grade 5 adverse events, n (%) | 3 (5.2) | 3 (5.4) | 6 (10.2) |
| Permanent discontinuations due to adverse events, n (%) | 8 (13.8) | 4 (7.1) | 5 (8.5) |
| Temporary discontinuations due to adverse events, n (%) | 18 (31.0) | 19 (33.9) | 26 (44.1) |
| Dose reductions due to adverse events, n (%) | 15 (25.9) | 16 (28.6) | 23 (39.0) |
| Concomitant drug treatment for adverse events of interest in the first 8 weeks of treatment | |||
| SDAEI, diarrhea, and mucositis, n (%) | 43 (74.1) | 37 (66.1) | 49 (83.1) |
| SDAEI, n (%) | 38 (65.5) | 28 (50.0) | 31 (52.5) |
| Diarrhea, n (%) | 36 (62.1) | 26 (46.4) | 41 (69.5) |
| Mucositis, n (%) | 14 (24.1) | 18 (32.1) | 17 (28.8) |
| Diarrhea burden index in the first 8 weeks of treatment | |||
| Diarrhea burden index, mean (standard deviation) | 2.3 (2.27) | 1.9 (1.55) | 2.4 (2.55) |
| Mean difference in diarrhea burden index (95% CI), P value | |||
| Doxycycline versus placebo | −0.5 (−1.2, 0.3), P = 0.198 | ||
| Alclometasone + probiotic versus placebo | 0.1 (−0.8, 1.0), P = 0.860 | ||
| Alclometasone + probiotic versus doxycycline | 0.5 (−0.2, 1.3), P = 0.164 | ||
aRelative dose intensity is defined as the total actual received dose during the first 8 weeks from the date of first dacomitinib dose divided by (45 mg dacomitinib × 56 days).
Diarrhea burden index is defined as the sum of daily maximum CTCAE grade of diarrhea AE patient experienced over day 1 to day 56, regardless of dosing interruption and/or missed dose. The maximum CTCAE grade of diarrhea is 0 for a day if no diarrhea AE was experienced on the day.
SDAEI, select dermatologic adverse events of interest; CI, confidence interval; CTCAE, common terminology criteria for adverse events; AE, adverse event.