Table 4.
Incidence rate (IR) per 100 person-years of liver chemistry (LC) elevation among renal cell carcinoma with selected treatment as first line of therapy, Altos and Veterans Affairs (VA)
| LC test and threshold | Pazopanib | Bevacizumab | Sorafenib | Sunitinib | ||||
|---|---|---|---|---|---|---|---|---|
| Altos | VA | Altos | VA | Altos | VA | Altos | VA | |
| ALT ≥2x ULN | ||||||||
| N cases/total | 3/57 | 24/123 | 2/35 | 2/48 | 1/24 | 12/136 | 24/221 | 37/500 |
| IR (95 % CI) | 20.8 (15.8, 27) | 50.7 (42.2, 60.5) | 13.4 (9.3, 18.6) | 9.0 (6.6, 11.9) | 13.4 (8.6, 19.9) | 19.9 (16.7, 23.5) | 44.2 (38.6, 50.5) | 15.4 (14.0, 16.8) |
| ALT ≥3x ULN | ||||||||
| N cases/total | 4/59 | 20/125 | 2/36 | 2/49 | 1/24 | 6/139 | 7/224 | 16/513 |
| IR (95 % CI) | 27.2 (20.7, 35.0) | 39.4 (32.8, 46.9) | 13.3 (9.3, 18.4) | 8.6 (6.4, 11.4) | 13.3 (8.5, 19.8) | 9.2 (7.8, 10.9) | 11.9 (10.4, 13.6) | 6.3 (5.8, 6.9) |
| ALT ≥8x ULN | ||||||||
| N cases/total | 2/60 | 2/127 | 1/37 | 0/49 | 0/24 | 0/140 | 0/230 | 4/516 |
| IR (95 % CI) | 13.0 (9.9, 16.8) | 3.4 (2.9, 4.1) | 6.6 (4.7, 9.1) | 0 (0, 18.7) | 0 (0, 57.3) | 0 (0, 6.6) | 0 (0, 7.0) | 1.6 (1.4, 1.7) |
| Bilirubin >1x ULN | ||||||||
| N cases/total | 8/59 | 20/122 | 2/37 | 12/51 | 2/25 | 21/132 | 17/219 | 97/508 |
| IR (95 % CI) | 54.1 (41.2, 69.7) | 39.7 (33.0, 47.4) | 13.4 (9.4, 18.5) | 54.4 (40.5, 71.5) | 29.0 (18.7, 42.8) | 38.1 (31.9, 45.2) | 29.3 (25.5, 33.4) | 43.7 (40.0, 47.6) |
| Bilirubin ≥1.5x ULN to 1.99x ULN | ||||||||
| N cases/total | 2/60 | 8/126 | 1/37 | 2/51 | 0/26 | 10/142 | 5/226 | 29/520 |
| IR (95 % CI) | 12.6 (9.6, 16.2) | 14.7 (12.3, 17.5) | 6.6 (4.7, 9.1) | 8.1 (6, 10.6) | 0 (0, 55.8) | 15.3 (12.9, 18.1) | 8.3 (7.2, 9.4) | 11.4 (10.4, 12.4) |
| Bilirubin ≥2x ULN | ||||||||
| N cases/total | 1/60 | 3/126 | 1/37 | 1/51 | 0/26 | 9/142 | 3/231 | 26/523 |
| IR (95 % CI) | 6.3 (4.8, 8.1) | 5.4 (4.5, 6.5) | 6.6 (4.6, 9.1) | 4.0 (3.0, 5.2) | 0 (0, 55.8) | 13.7 (11.5, 16.1) | 4.8 (4.2, 5.5) | 10.0 (9.1, 10.8) |
| Possible Hy’s law | ||||||||
| N cases/total | 0/60 | 0/115 | 0/37 | 0/47 | 0/25 | 1/126 | 0/231 | 2/477 |
| IR (95 % CI) | 0 (0, 27.1) | 0 (0, 24.9) | 0 (0, 28.6) | 0 (0, 24.9) | 0 (0, 56.3) | 1.6 (1.4, 1.9) | 0 (0, 7.0) | 0.8 (4.5, 6.7) |
Possible Hy’s law: the combination of LC elevations indicative of possible Hy’s law was defined as ALT or AST ≥3x ULN, total bilirubin ≥2x ULN and ALP <2x ULN
ALP alkaline phosphatase, ALT alanine aminotransferase, AST aspartate aminotransferase, CI confidence interval, SD standard deviation, ULN upper limit of normal