Table 3 Trametinib Related Adverse Events ≥10% of study patients in descending order of frequency of occurrence
Normal (Norm) (2 mg) | Mild (2 mg) | Moderate (Mod) DL1 (1.5 mg) | Moderate (Mod) DL+1 (2 mg) | Severe (Sev) DL1 (1 mg) | Severe (Sev) DL+1 (1.5 mg) | Total Patients | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Number of patients (Safety evaluable patients with at least one dose of trametinib) | 17 | 7 | 3 | 6 | 9 | 2 | |||||||||||||
Median Cycle of Treatment Completed (Range) | 2 (0, 18) | 1 (0, 6) | 3 (2, 3) | 1 (0, 2) | 1 (0, 5) | 0.5 (0, 1) | |||||||||||||
Adverse Event (Treatment Related), Grade | All | G1-2 | G ≥ 3 | All | G1-2 | G ≥ 3 | All | G1-2 | G ≥ 3 | All | G1-2 | G ≥ 3 | All | G1-2 | G ≥ 3 | All | G1-2 | G ≥ 3 | |
Acneiform rash | 9 (53%) | 9 (53%) | 0 (0%) | 6 (86%) | 6 (86%) | 0 (0%) | 2 (67%) | 2 (67%) | 0 (0%) | 3 (50%) | 3 (50%) | 0 (0%) | 1 (11%) | 1 (11%) | 0 (0%) | 1 (50%) | 0 (0%) | 1 (50%) | 22 (50%) |
Nausea | 11 (65%) | 11 (65%) | 0 (0%) | 2 (29%) | 2 (29%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 2 (33%) | 2 (33%) | 0 (0%) | 1 (11%) | 1 (11%) | 0 (0%) | 1 (50%) | 1 (50%) | 0 (0%) | 17 (39%) |
Diarrhea | 9 (53%) | 7 (41%) | 2 (12%) | 2 (29%) | 2 (29%) | 0 (0%) | 1 (33%) | 1 (33%) | 0 (0%) | 2 (33%) | 2 (33%) | 0 (0%) | 2 (22%) | 2 (22%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 16 (36%) |
Fatigue | 10 (59%) | 8 (47%) | 2 (12%) | 1 (14%) | 1 (14%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 2 (33%) | 2 (33%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (50%) | 0 (0%) | 1 (50%) | 14 (32%) |
Aspartate aminotransferase increased | 10 (59%) | 9 (53%) | 1 (6%) | 1 (14%) | 1 (14%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (17%) | 1 (17%) | 0 (0%) | 1 (11%) | 1 (11%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 13 (30%) |
Anemia | 7 (41%) | 6 (35%) | 1 (6%) | 2 (29%) | 2 (29%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (11%) | 1 (11%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 10 (23%) |
Maculopapular rash | 5 (29%) | 3 (18%) | 2 (12%) | 2 (29%) | 2 (29%) | 0 (0%) | 3 (100%) | 3 (100%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (11%) | 1 (11%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 11 (23%) |
Thrombocytopenia | 6 (35%) | 5 (29%) | 1 (6%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 2 (33%) | 2 (33%) | 0 (0%) | 1 (11%) | 1 (11%) | 0 (0%) | 1 (50%) | 1 (50%) | 0 (0%) | 10 (23%) |
Alanine aminotransferase increased | 5 (29%) | 5 (29%) | 0 (0%) | 2 (29%) | 1 (14%) | 1 (14%) | 0 (0%) | 0 (0%) | 0 (0%) | 2 (33%) | 2 (33%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 9 (20%) |
Blood alkaline phosphatase increased | 7 (41%) | 7 (41%) | 0 (0%) | 2 (29%) | 2 (29%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 9 (20%) |
Hyponatremia | 5 (29%) | 3 (18%) | 2 (12%) | 2 (29%) | 2 (29%) | 0 (0%) | 1 (17%) | 1 (17%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (11%) | 1 (11%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 9 (20%) |
Vomiting | 4 (24%) | 4 (24%) | 0 (0%) | 4 (57%) | 4 (57%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (11%) | 1 (11%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 9 (20%) |
Hypertension | 5 (29%) | 4 (24%) | 1 (6%) | 2 (29%) | 2 (29%) | 0 (0%) | 1 (33%) | 1 (33%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 8 (18%) |
Hypomagnesemia | 5 (29%) | 5 (29%) | 0 (0%) | 3 (43%) | 3 (43%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 8 (18%) |
Decreased appetite | 5 (29%) | 5 (29%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 2 (33%) | 2 (33%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 7 (16%) |
Lymphopenia | 4 (24%) | 3 (18%) | 1 (6%) | 1 (14%) | 1 (14%) | 0 (0%) | 1 (33%) | 1 (33%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (11%) | 0 (0%) | 1 (11%) | 0 (0%) | 0 (0%) | 0 (0%) | 7 (16%) |
Peripheral Edema | 4 (24%) | 4 (24%) | 0 (0%) | 1 (14%) | 1 (14%) | 0 (0%) | 1 (33%) | 1 (33%) | 0 (0%) | 1 (17%) | 1 (17%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 7 (16%) |
Hypoalbuminemia | 5 (29%) | 4 (24%) | 1 (6%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (17%) | 1 (17%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 6 (14%) |
Mucositis | 2 (12%) | 2 (12%) | 0 (0%) | 2 (29%) | 2 (29%) | 0 (0%) | 1 (33%) | 1 (33%) | 0 (0%) | 1 (17%) | 1 (17%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 6 (14%) |
Cracked skin / fissure | 4 (24%) | 4 (24%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (17%) | 1 (17%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 5 (11%) |
Dysgeusia | 4 (24%) | 4 (24%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (33%) | 1 (33%) | 0 (0%) | 1 (17%) | 1 (17%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 5 (11%) |
Leucopenia | 3 (18%) | 3 (18%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (33%) | 1 (33%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (11%) | 1 (11%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 5 (11%) |
Dose interruption/reduction | 9 (53%) | 3 (43%) | 3 (100%) | 3 (50%) | 3 (33%) | 2 (100%) | 23 (52%) | ||||||||||||
Dose interruption/reduction due to TRAEs | 9 (53%) | 2 (29%) | 1 (33%) | 1 (11%) | 1 (11%) | 1 (50%) | 15 (43%) | ||||||||||||
Dose interruption/reduction due to non- TRAEs | 0 (0%) | 1(14%) | 2 (66%) | 1 (17%) | 2 (22%) | 1 (50%) | 7 (16%) | ||||||||||||
Treatment discontinuation due to TRAEs | 1 (6%) | 1 (14%) | 0 (0%) | 1 (33%) | 0 (0%) | 0 (0%) | 3 (7%) | ||||||||||||
Treatment discontinuation due to non-TRAEs | 1 (6%) | 0 (0%) | 0 (0%) | 3 (50%) | 5 (56%) | 1 (50%) | 10 (23%) | ||||||||||||
Death related to TRAEs | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | ||||||||||||
Any SAE | 10 (59%) | 4 (57%) | 3 (100%) | 5 (83%) | 8 (89%) | 2 (100%) | 32 (73%) | ||||||||||||
Treatment related SAE | 7 (41%) | 2 (29%) | 1 (33%) | 0 (0%) | 0 (0%) | 0 (0%) | 10 (23%) | ||||||||||||