Refametinib and sorafenib combination in advanced cancer

Supplementary Table 2. Grade 3 or 4 adverse events possibly related to refametinib or sorafenib, occurring in ≥2 patients in either cohort

Non-HCC patients / HCC patients
Gradea / Dose-escalation cohort
(n=32) / MTD expansion
cohort
(n=11) / Total
(N=43) / MTD expansion
cohort
(n=19)
Possibly related to refametinib, n (%)
Patients with ≥1 AE / 3 / 14 (43.8) / 4 (36.4) / 18 (41.9) / 9 (47.4)
Patients with ≥1 AE / 4 / 1 (3.1)a / 0 / 1 (2.3)b / 3 (15.8)c
Diarrhea / 3 / 4 (12.5) / 3 (27.3) / 7 (16.3) / 4 (21.1)
Dermatitis acneiform / 3 / 0 / 1 (9.1) / 1 (2.3) / 4 (21.1)
Rash / 3 / 3 (9.4) / 0 / 3 (7.0) / 0
Fatigue / 3 / 2 (6.3) / 0 / 2 (4.7) / 2 (10.5)
Increased AST / 3 / 2 (6.3) / 0 / 2 (4.7) / 5 (26.3)
Increased blood ALP / 3 / 3 (9.4) / 0 / 3 (7.0) / 0
Hypokalemia / 3 / 1 (3.1) / 1 (9.1) / 2 (4.7) / 0
Left ventricular dysfunction / 3 / 2 (6.3) / 0 / 2 (4.7) / 0
Possibly related to sorafenib, n (%)
Patients with ≥1 AE / 3 / 17 (53.1) / 5 (45.5) / 22 (51.2) / 13 (68.4)
Patients with ≥1 AE / 4 / 1 (3.1)a / 0 / 1 (2.3)b / 2 (10.5)d
Diarrhea / 3 / 4 (12.5) / 3 (27.3) / 7 (16.3) / 5 (26.3)
Dermatitis acneiform / 3 / 0 / 0 / 0 / 5 (26.3)
Rash / 3 / 3 (9.4) / 0 / 3 (7.0) / 0
Fatigue / 3 / 2 (6.3) / 0 / 2 (4.7) / 2 (10.5)
Increased AST / 3 / 3 (9.4) / 0 / 3 (7.0) / 5 (26.3)
Increased blood ALP / 3 / 3 (9.4) / 0 / 3 (7.0) / 0
Hypokalemia / 3 / 1 (3.1) / 1 (9.1) / 2 (4.7) / 0
Left ventricular dysfunction / 3 / 2 (6.3) / 0 / 2 (4.7) / 1 (5.3)
Hypertension / 3 / 1 (3.1) / 0 / 1 (2.3) / 2 (10.5)
Anemia / 3 / 2 (6.3) / 0 / 2 (4.7) / 0

aAEs assessed by National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0.
bGrade 4 AE was subarachnoid hemorrhage.
cGrade 4 AEs were hypokalemia, hyperuricemia, and thrombocytopenia.
dGrade 4 AEs were hypokalemia and thrombocytopenia.
Abbreviations: AE, adverse event; ALP, alkaline phosphatase; AST, aspartate aminotransferase; HCC, hepatocellular carcinoma; MTD,maximum tolerated dose.