Characteristics and management of ALT and AST TEAEs
| Parameter . | ALT elevation (n = 99) . | AST elevation (n = 81) . | ALT or AST elevation (n = 112) . |
|---|---|---|---|
| Median time to first event (range), d | 30 (6-841) | 33 (1-1400) | 33.5 (1-1400) |
| Median duration of event (range), d | 21 (1-1714) | 20 (1-803) | 21.0 (1-1714) |
| Events resolved, n (%) | 84 (85) | 69 (85) | 94 (84) |
| Event management, n (%) | |||
| Received dose reduction | 17 (17) | 7 (9) | 20 (18) |
| Received dose interruption | 39 (39) | 28 (35) | 39 (35) |
| No rechallenge | 4 (10) | 7 (25) | 4 (10) |
| Rechallenge | 35 (90) | 21 (75) | 35 (90) |
| Successful rechallenge* | 26 (74) | 19 (90) | 26 (74) |
| Unsuccessful rechallenge† | 9 (26) | 2 (10) | 9 (26) |
| Received concurrent medication‡ | 12 (12) | 10 (12) | 14 (13) |
| Permanent treatment discontinuation due to event§ | 12/570 (2) | 4/570 (1) | 13/570 (2) |
| Parameter . | ALT elevation (n = 99) . | AST elevation (n = 81) . | ALT or AST elevation (n = 112) . |
|---|---|---|---|
| Median time to first event (range), d | 30 (6-841) | 33 (1-1400) | 33.5 (1-1400) |
| Median duration of event (range), d | 21 (1-1714) | 20 (1-803) | 21.0 (1-1714) |
| Events resolved, n (%) | 84 (85) | 69 (85) | 94 (84) |
| Event management, n (%) | |||
| Received dose reduction | 17 (17) | 7 (9) | 20 (18) |
| Received dose interruption | 39 (39) | 28 (35) | 39 (35) |
| No rechallenge | 4 (10) | 7 (25) | 4 (10) |
| Rechallenge | 35 (90) | 21 (75) | 35 (90) |
| Successful rechallenge* | 26 (74) | 19 (90) | 26 (74) |
| Unsuccessful rechallenge† | 9 (26) | 2 (10) | 9 (26) |
| Received concurrent medication‡ | 12 (12) | 10 (12) | 14 (13) |
| Permanent treatment discontinuation due to event§ | 12/570 (2) | 4/570 (1) | 13/570 (2) |
Successful rechallenge includes patients who did not experience subsequent ALT or AST AEs (n = 4 and n = 6, respectively) or experienced subsequent ALT and AST AEs that did not lead to treatment discontinuation (n = 22 and n = 13).
Unsuccessful rechallenge indicates treatment discontinuation due to ALT or AST elevation following rechallenge with bosutinib.
Concurrent medications used for management of ALT and/or AST elevations included essential phospholipids, ursodiol, steroids, S-adenosylmethionine, milk thistle extract, and glycyrrhizic acid. Patients may have received ≥1 medication.
Includes patients with no rechallenge or unsuccessful rechallenge following dose interruption, as well as those who discontinued treatment due to ALT or AST elevation without dose interruption.