Table 1.
Hepatotoxicity results of phase III trials in patients with melanoma undergoing immunotherapy
| Study | Type of ICPI (dosing schedule) |
Cancer setting | AST (n/N, %) All grades |
AST (n/N, %) Grades 3–4 |
ALT (n/N, %) All grades |
ALT (n/N, %) Grades 3–4 |
Hepatitis (n/N, %) All grades |
Hepatitis (n/N, %) Grades 3–4 |
| Eggermont et al (EORTC 18071)64 |
Ipilimumab (10 mg/kg every 3 weeks for four doses, then every 3 months for up to 3 years) |
Adjuvant | 78/471 (16.5) | 20/471 (4.2) | 102/471(21) | 25/471 (5) | ||
| Weber et al 65 |
Nivolumab (3 mg/kg every 2 wks for up to 1 year) |
Adjuvant | 25/452 (5.5) | 2/452 (0.4) | 28/452 (6.2) | 5/452 (1.1) | ||
| Ipilimumab (10 mg/kg every 3 wks for four doses and then every 12 wks for up to 1 year) | Adjuvant | 60/453 (13.2) | 19/453 (4.2) | 66/453 (14.6) | 26/453 (5.7) | |||
| Tarhini et al (North American Intergroup E1609)66 |
Ipilimumab (3 mg/kg every 3 wks for four doses, followed by the same dose every 12 wks for up to four additional doses) |
Adjuvant | 96/516 (18.6) | 16/516 (3.1) | ||||
| Ipilimumab (10 mg/kg every 3 wks for four doses, followed by the same dose every 12 wks for up to four additional doses) |
Adjuvant | 163/503 (32.4) | 40/503 (8.0) | |||||
| Eggermont et al (KEYNOTE-054)8 |
Pembrolizumab (200 mg every 3 wks for up to 1 year) |
Adjuvant | 9/509 (1.8) | 7/502 (1.4) | ||||
| Hodi et al 67 |
Ipilimumab (3 mg/kg every 3 wks for four doses) |
Metastatic | 1/131 (0.8) | 0/131 (0) | 2/131 (1.5) | 0/131 (0) | 1/131 (0.8) | 0/131 (0) |
| Robert et al 21 |
Ipilimumab (10 mg/kg plus dacarbazine 850 mg/m2) |
Metastatic | 66/247 (26.7) | 43/247 (17.4) | 72/247 (29.1) | 51 (20.7) | 4/247 (1.6) | 3/247 (1.2) |
| Larkin et al (CheckMate067)9 10 |
Nivolumab (1 mg/kg every 3 wks)/ipilimumab (3 mg/kg every 3 wks) for four doses, followed by 3 mg/kg of nivolumab every 2 weeks for cycle three and beyond | Metastatic | 48/313 (15.3) | 19/313 (6.1) | 55/313 (17.6) | 26/313 (8.3) | 10/313 (3.2) | 8/313 (2.6) |
| Ipilimumab (3 mg/kg every 3 wks for four doses) |
Metastatic | 11/311 (3.5) | 2/311 (0.6) | 12/311 (3.9) | 5/311 (1.6) | 3/311 (0.9) | 0/311 (0) | |
| Nivolumab (3 mg/kg every 2 wks until PD) |
Metastatic | 12/313 (3.8) | 3/313 (1) | 12/313 (3.8) | 4/313 (1.3) | 1/313 (<1) | 1/313 (<1) | |
| Robert et al (KEYNOTE-006)7 |
Pembrolizumab (200 mg every 3 wks for up to 1 year) |
Metastatic | 5/277 (1.8) | 5/277 (1.8) | ||||
| Ipilimumab (10 mg/kg every 3 wks for four doses and then every 12 wks) |
Metastatic | 3/256 (1.2) | 1/256 (0.4) | |||||
| Weber et al (CheckMate037)23 | Nivolumab (3 mg/kg every 2 wks until PD) |
Metastatic (previously treated) |
12/268 (4.5), hepatic TRAEs | 2/268 (0.7), hepatic TRAEs |
ALT, alanine aminotransferase; AST, aspartate aminotransferase; PD, progressive disease; TRAEs, treatment-related adverse events; wk, week.