Table 2.
Adverse events in patients enrolled prior to the trial amendment (n = 6) and in patients enrolled after the trial amendment (n = 10).
| Adverse Events (n (%)) | Patients Enrolled Prior to Trial Amendment n = 6 |
Patients Enrolled after Trial Amendment n = 10 |
||
|---|---|---|---|---|
| All-Grade | Grade 3–4 | All-Grade | Grade 3–4 | |
| All AE | 6 (100.0) | 3 (50.0) | 10 (100.0) | 4 (40.0) |
| Acneiform rash | 6 (100.0) * | 0 | 3 (30.0) ° | 0 |
| Acneiform rash leading to temporary treatment interruption | 6 (100.0) | 0 | 0 | 0 |
| Acneiform rash leading to add-on of low-dose dabrafenib | 6 (100.0) | 0 | NA | NA |
| Fatigue | 4 (66.7) | 1 (16.7) | 4 (40.0) | 0 |
| Creatine phosphokinase increase | 4 (66.7) | 0 | 6 (60.0) | 0 |
| Lipase increased | 3 (50.0) | 0 | 3 (30.0) | 0 |
| Anemia | 3 (50.0) | 0 | 2 (20.0) | 0 |
| Fever | 3 (50.0) | 0 | 1 (10.0) | 1 (10.0) |
| Arterial hypertension | 2 (33.3) | 0 | 3 (30.0) | 0 |
| Aspartate aminotransferase increase | 2 (33.3) | 0 | 3 (30.0) | 1 (10.0) |
| Central serous retinopathy | 2 (33.3) | 0 | 1 (10.0) | 0 |
| Diarrhea | 2 (33.3) | 0 | 4 (40.0) | 0 |
| Lymphocyte count decreased | 2 (33.3) | 0 | 1 (10.0) | 0 |
| Nausea | 2 (33.3) | 0 | 3 (30.0) | 0 |
| Hyperkalemia | 1 (16.7) | 1 (16.7) | 0 | 0 |
| Hyponatremia | 1 (16.7) | 1 (16.7) | 3 (30.0) | 2 (20.0) |
| Idiopathic thrombocytopenic purpura | 1 (16.7) | 1 (16.7) | 0 | 0 |
| Lung infection | 1 (16.7) | 1 (16.7) | 0 | 0 |
| Syncope | 1 (16.7) | 1 (16.7) | 1 (10.0) | 1 (10.0) |
| Abdominal pain | 1 (16.7) | 0 | 1 (10.0) | 0 |
| Alanine aminotransferase increase | 1 (16.7) | 0 | 3 (30.0) | 2 (20.0) |
| Anorexia | 1 (16.7) | 0 | 2 (20.0) | 0 |
| Atrial fibrillation | 1 (16.7) | 0 | 0 | 0 |
| Blot bleed retina | 1 (16.7) | 0 | 0 | 0 |
| Chills | 1 (16.7) | 0 | 2 (20.0) | 0 |
| Cough | 1 (16.7) | 0 | 0 | 0 |
| Edema lower limbs | 1 (16.7) | 0 | 1 (10.0) | 0 |
| Eosinophilia | 1 (16.7) | 0 | 0 | 0 |
| Ejection fraction decreased | 1 (16.7) | 0 | 1 (10.0) | 1 (10.0) |
| Eosinophil count increased | 1 (16.7) | 0 | 0 | 0 |
| Heart failure | 1 (16.7) | 0 | 0 | 0 |
| Hypoalbuminemia | 1 (16.7) | 0 | 0 | 0 |
| Ileus | 1 (16.7) | 0 | 0 | 0 |
| Inflammatory syndrome | 1 (16.7) | 0 | 0 | 0 |
| Maculopapular rash | 1 (16.7) | 0 | 1 (10.0) | 0 |
| Malaise | 1 (16.7) | 0 | ||
| Neutrophil count decreased | 1 (16.7) | 0 | 3 (30.0) | 0 |
| Occlusion retinal arteriolus | 1 (16.7) | 0 | 0 | 0 |
| Operculum retinae | 1 (16.7) | 0 | 0 | 0 |
| Paronychia | 1 (16.7) | 0 | 0 | 0 |
| Platelet count decreased | 1 (16.7) | 0 | 2 (20.0) | 0 |
| Radiation pneumonitis | 1 (16.7) | 0 | 0 | 0 |
| White blood cell count decreased | 1 (16.7) | 0 | 2 (20.0) | 1 (10.0) |
| Vomiting | 0 | 0 | 3 (30.0) | 0 |
| Acute kidney injury | 0 | 0 | 2 (20.0) | 0 |
| Muscle cramps | 0 | 0 | 2 (20.0) | 0 |
| Gamma glutamyl transferase increased | 0 | 0 | 1 (10.0) | 1 (10.0) |
| Pneumonitis | 0 | 0 | 1 (10.0) | 1 (10.0) |
| Pulmonary embolism | 0 | 0 | 1 (10.0) | 1 (10.0) |
| Alkaline phosphatase increased | 0 | 0 | 1 (10.0) | 0 |
| Arthralgia | 0 | 0 | 1 (10.0) | 0 |
| Bronchopulmonary hemorrhage | 0 | 0 | 1 (10.0) | 0 |
| Dry mouth | 0 | 0 | 1 (10.0) | 0 |
| Dyspepsia | 0 | 0 | 1 (10.0) | 0 |
| Headache | 0 | 0 | 1 (10.0) | 0 |
| Hypokalemia | 0 | 0 | 1 (10.0) | 0 |
| Neuropathic pain | 0 | 0 | 1 (10.0) | 0 |
| Posterior vitreous detachment | 0 | 0 | 1 (10.0) | 0 |
| Retinal pigment epithelial detachment | 0 | 0 | 1 (10.0) | 0 |
| Retinoschisis | 0 | 0 | 1 (10.0) | 0 |
| Squamous rash | 0 | 0 | 1 (10.0) | 0 |
| Skin infection | 0 | 0 | 1 (10.0) | 0 |
| Urinary tract infection | 0 | 0 | 1 (10.0) | 0 |
| Serious AE | 3 (50.0) | 2 (33.3) | 5 (50.0) | 4 (40.0) |
| AE leading to dose reduction | 3 (50.0) | 0 | 5 (50.0) | 4 (40.0) |
| AE leading to temporary treatment interruption | 6 (100.0) | 2 (33.3) | 6 (60.0) | 4 (40.0) |
| AE leading to permanent treatment interruption | 0 | 0 | 0 | 0 |
* Five patients with grade 2 and one patient with grade 1; ° three patients with grade 1. Abbreviations: AE: adverse events; NA: not applicable.