Treatment modifications and discontinuations due to AEs
| Parameter, n (%) or median (range) . | CP2L . | CP3L . | ADV (n = 166) . | Total (n = 570) . | |||||
|---|---|---|---|---|---|---|---|---|---|
| IM-R (n = 196) . | IM-I (n = 90)* . | Total (n = 286) . | IM-R/I + D-R (n = 38) . | IM-R/I + D-I (n = 50)* . | IM-R/I + N-R (n = 26) . | Total† (n = 118) . | |||
| Patients with ≥1 dose reduction‡,§ | 87 (44) | 52 (58) | 139 (49) | 13 (34) | 32 (64) | 13 (50) | 59 (50) | 57 (34) | 255 (45) |
| No. dose reductions per patient|| | |||||||||
| 1 | 45 (23) | 33 (37) | 78 (27) | 10 (26) | 16 (32) | 10 (39) | 36 (31) | 32 (19) | 146 (26) |
| 2 | 37 (19) | 15 (17) | 52 (18) | 2 (5) | 13 (26) | 2 (8) | 18 (15) | 21 (13) | 91 (16) |
| ≥3 | 5 (3) | 4 (4) | 9 (3) | 1 (3) | 3 (6) | 1 (4) | 5 (4) | 4 (2) | 18 (3) |
| Patients with ≥1 dose interruption | 130 (66) | 75 (83) | 205 (72) | 19 (50) | 40 (80) | 16 (62) | 78 (66) | 85 (51) | 368 (65) |
| No. dose interruptions per patient | |||||||||
| 1 | 51 (26) | 34 (38) | 85 (30) | 11 (29) | 14 (28) | 6 (23) | 32 (27) | 40 (24) | 157 (28) |
| 2 | 33 (17) | 21 (23) | 54 (19) | 3 (8) | 11 (22) | 5 (19) | 19 (16) | 21 (13) | 94 (17) |
| 3 | 21 (11) | 7 (8) | 28 (10) | 1 (3) | 5 (10) | 2 (8) | 9 (8) | 10 (6) | 47 (8) |
| ≥4 | 25 (13) | 13 (14) | 38 (13) | 4 (11) | 10 (20) | 3 (12) | 18 (15) | 14 (8) | 70 (12) |
| Median cumulative duration of interruption (range), d | 21.5 (1-582) | 22.0 (1-429) | 22.0 (1-582) | 24.0 (1-144) | 29.5 (1-181) | 28.0 (1-150) | 27.0 (1-181) | 20.0 (1-257) | 22.0 (1-582) |
| Early (≤4 wk) interruptions | 53 (27) | 38 (42) | 91 (32) | 8 (21) | 19 (38) | 5 (19) | 32 (27) | 52 (31) | 175 (31) |
| Treatment discontinuation¶ | 30 (15) | 34 (38) | 64 (22) | 6 (16) | 20 (40) | 3 (12) | 29 (25) | 30 (18) | 123 (22) |
| Thrombocytopenia# | 6 (3) | 11 (12) | 17 (6) | 1 (3) | 7 (14) | 0 | 8 (7) | 5 (3) | 30 (5) |
| Increased ALT | 3 (2) | 4 (4) | 7 (2) | 0 | 1 (2) | 2 (8) | 3 (3) | 3 (2) | 13 (2) |
| Neutropenia# | 2 (1) | 6 (7) | 8 (3) | 3 (8) | 1 (2) | 1 (4) | 5 (4) | 0 | 13 (2) |
| Diarrhea | 3 (2) | 1 (1) | 4 (1) | 1 (3) | 1 (2) | 0 | 2 (2) | 0 | 6 (1) |
| Vomiting | 1 (1) | 2 (2) | 3 (1) | 1 (3) | 2 (4) | 0 | 3 (3) | 1 (1) | 7 (1) |
| Increased AST | 1 (1) | 1 (1) | 2 (1) | 0 | 0 | 1 (4) | 1 (1) | 1 (1) | 4 (1) |
| Cardiac failure | 1 (1) | 0 | 1 (<1) | 0 | 2 (4) | 0 | 2 (2) | 0 | 3 (1) |
| Dyspnea | 0 | 1 (1) | 1 (<1) | 0 | 1 (2) | 0 | 1 (1) | 2 (1) | 4 (1) |
| Pleural effusion | 0 | 1 (1) | 1 (<1) | 0 | 1 (2) | 0 | 1 (1) | 2 (1) | 4 (1) |
| Pulmonary fibrosis | 0 | 1 (1) | 1 (<1) | 0 | 0 | 0 | 0 | 2 (1) | 3 (1) |
| Anemia# | 0 | 2 (2) | 2 (1) | 1 (3) | 1 (2) | 0 | 2 (2) | 1 (1) | 5 (1) |
| Myocardial infarction | 0 | 0 | 0 | 1 (3) | 0 | 0 | 1 (1) | 1 (1) | 2 (<1) |
| Pneumonia | 1 (1) | 0 | 1 (<1) | 0 | 0 | 0 | 0 | 1 (1) | 2 (<1) |
| Rash | 1 (1) | 2 (2) | 3 (1) | 0 | 0 | 0 | 0 | 0 | 3 (1) |
| Pericardial effusion | 0 | 0 | 0 | 0 | 1 (2) | 0 | 1 (1) | 3 (2) | 4 (1) |
| Parameter, n (%) or median (range) . | CP2L . | CP3L . | ADV (n = 166) . | Total (n = 570) . | |||||
|---|---|---|---|---|---|---|---|---|---|
| IM-R (n = 196) . | IM-I (n = 90)* . | Total (n = 286) . | IM-R/I + D-R (n = 38) . | IM-R/I + D-I (n = 50)* . | IM-R/I + N-R (n = 26) . | Total† (n = 118) . | |||
| Patients with ≥1 dose reduction‡,§ | 87 (44) | 52 (58) | 139 (49) | 13 (34) | 32 (64) | 13 (50) | 59 (50) | 57 (34) | 255 (45) |
| No. dose reductions per patient|| | |||||||||
| 1 | 45 (23) | 33 (37) | 78 (27) | 10 (26) | 16 (32) | 10 (39) | 36 (31) | 32 (19) | 146 (26) |
| 2 | 37 (19) | 15 (17) | 52 (18) | 2 (5) | 13 (26) | 2 (8) | 18 (15) | 21 (13) | 91 (16) |
| ≥3 | 5 (3) | 4 (4) | 9 (3) | 1 (3) | 3 (6) | 1 (4) | 5 (4) | 4 (2) | 18 (3) |
| Patients with ≥1 dose interruption | 130 (66) | 75 (83) | 205 (72) | 19 (50) | 40 (80) | 16 (62) | 78 (66) | 85 (51) | 368 (65) |
| No. dose interruptions per patient | |||||||||
| 1 | 51 (26) | 34 (38) | 85 (30) | 11 (29) | 14 (28) | 6 (23) | 32 (27) | 40 (24) | 157 (28) |
| 2 | 33 (17) | 21 (23) | 54 (19) | 3 (8) | 11 (22) | 5 (19) | 19 (16) | 21 (13) | 94 (17) |
| 3 | 21 (11) | 7 (8) | 28 (10) | 1 (3) | 5 (10) | 2 (8) | 9 (8) | 10 (6) | 47 (8) |
| ≥4 | 25 (13) | 13 (14) | 38 (13) | 4 (11) | 10 (20) | 3 (12) | 18 (15) | 14 (8) | 70 (12) |
| Median cumulative duration of interruption (range), d | 21.5 (1-582) | 22.0 (1-429) | 22.0 (1-582) | 24.0 (1-144) | 29.5 (1-181) | 28.0 (1-150) | 27.0 (1-181) | 20.0 (1-257) | 22.0 (1-582) |
| Early (≤4 wk) interruptions | 53 (27) | 38 (42) | 91 (32) | 8 (21) | 19 (38) | 5 (19) | 32 (27) | 52 (31) | 175 (31) |
| Treatment discontinuation¶ | 30 (15) | 34 (38) | 64 (22) | 6 (16) | 20 (40) | 3 (12) | 29 (25) | 30 (18) | 123 (22) |
| Thrombocytopenia# | 6 (3) | 11 (12) | 17 (6) | 1 (3) | 7 (14) | 0 | 8 (7) | 5 (3) | 30 (5) |
| Increased ALT | 3 (2) | 4 (4) | 7 (2) | 0 | 1 (2) | 2 (8) | 3 (3) | 3 (2) | 13 (2) |
| Neutropenia# | 2 (1) | 6 (7) | 8 (3) | 3 (8) | 1 (2) | 1 (4) | 5 (4) | 0 | 13 (2) |
| Diarrhea | 3 (2) | 1 (1) | 4 (1) | 1 (3) | 1 (2) | 0 | 2 (2) | 0 | 6 (1) |
| Vomiting | 1 (1) | 2 (2) | 3 (1) | 1 (3) | 2 (4) | 0 | 3 (3) | 1 (1) | 7 (1) |
| Increased AST | 1 (1) | 1 (1) | 2 (1) | 0 | 0 | 1 (4) | 1 (1) | 1 (1) | 4 (1) |
| Cardiac failure | 1 (1) | 0 | 1 (<1) | 0 | 2 (4) | 0 | 2 (2) | 0 | 3 (1) |
| Dyspnea | 0 | 1 (1) | 1 (<1) | 0 | 1 (2) | 0 | 1 (1) | 2 (1) | 4 (1) |
| Pleural effusion | 0 | 1 (1) | 1 (<1) | 0 | 1 (2) | 0 | 1 (1) | 2 (1) | 4 (1) |
| Pulmonary fibrosis | 0 | 1 (1) | 1 (<1) | 0 | 0 | 0 | 0 | 2 (1) | 3 (1) |
| Anemia# | 0 | 2 (2) | 2 (1) | 1 (3) | 1 (2) | 0 | 2 (2) | 1 (1) | 5 (1) |
| Myocardial infarction | 0 | 0 | 0 | 1 (3) | 0 | 0 | 1 (1) | 1 (1) | 2 (<1) |
| Pneumonia | 1 (1) | 0 | 1 (<1) | 0 | 0 | 0 | 0 | 1 (1) | 2 (<1) |
| Rash | 1 (1) | 2 (2) | 3 (1) | 0 | 0 | 0 | 0 | 0 | 3 (1) |
| Pericardial effusion | 0 | 0 | 0 | 0 | 1 (2) | 0 | 1 (1) | 3 (2) | 4 (1) |
Abbreviations are explained in Table 1.
The subgroups of patients with intolerance to prior TKI therapy.
Includes patients (n = 4) in whom prior imatinib therapy failed and who were intolerant to prior nilotinib therapy or resistant or intolerant to prior nilotinib and dasatinib therapy (because of low n, data not shown separately).
Dose reduction defined as a decrease in the dose level from the previous dose level administered.
For patients who started bosutinib treatment at a dose of 500 mg per day, dose could have been reduced to 400 mg per day because of toxicity and then subsequently escalated to 500 mg per day or reduced further to 300 mg per day. Patients whose dose was escalated to 500 mg per day could have had another dose reduction due to toxicity at another time; therefore, patients could have had multiple dose reductions to 400 or 300 mg per day.
Subcategory percentages may not add to the total due to rounding.
All AEs leading to treatment discontinuation in ≥1.0% of patients in the CP2L, CP3L, or ADV cohorts are shown in the table.
Individual hematologic AEs were clustered with the related terms from investigations.