Table 1.
Toxicities (%) associated with bosutinib 500 mg once-daily treatment in patients with CP CML with resistance or intolerance to prior imatinib and other TKIs [5, 6, 9]
| CP 2La |
CP 3Lb |
|||
|---|---|---|---|---|
| (n = 286) |
(n = 119) |
|||
| All Grade | Grade 3/4 | All Grade | Grade 3/4 | |
| TEAEsc | ||||
| Gastrointestinal | ||||
| Diarrhea | 86 | 10 | 83 | 9 |
| Nausea | 46 | 1 | 48 | 1 |
| Vomiting | 37 | 4 | 38 | 1 |
| Abdominal pain | 26 | 2 | 24 | 1 |
| Constipation | 14 | <1 | 13 | 0 |
| Musculoskeletal | ||||
| Arthralgia | 16 | 1 | 18 | 1 |
| Back pain | 14 | <1 | 12 | 3 |
| Extremity pain | 11 | 1 | – | – |
| Respiratory | ||||
| Cough | 22 | 0 | 22 | 0 |
| Pleural effusion | 8 | 2 | 17 | 5 |
| Dyspnea | 12 | 1 | 12 | 2 |
| General/other | ||||
| Rash | 36 | 9 | 28 | 3 |
| Fatigue | 26 | 1 | 24 | 2 |
| Headache | 19 | 0 | 27 | 3 |
| Pyrexia | 26 | 1 | 15 | 0 |
| Decreased appetite | 14 | 1 | 13 | 1 |
| Nasopharyngitis | 13 | 0 | 12 | 0 |
| Dizziness | 9 | 0 | 15 | 0 |
| Blood creatinine increased | 8 | <1 | 13 | 0 |
| Asthenia | 14 | 2 | − | – |
| Peripheral edema | 11 | <1 | – | – |
| Hypertension | 7 | 2 | – | – |
| Hematologicd | ||||
| Thrombocytopenia | 42 | 26 | 39 | 26 |
| Anemia | 27 | 11 | 20 | 7 |
| Neutropenia | 16 | 9 | 21 | 16 |
| Leukopenia | 12 | 5 | – | – |
| Cardiac eventse | 10 | 5 | 12 | 5 |
| Vascular eventsf | 8 | 4 | 6 | 3 |
| Laboratory abnormalities | ||||
| Nonhematologic | ||||
| Increased ALT/AST | – | 11/− | – | 6/3 |
| Increased lipase | – | 10 | – | – |
| Hyperglycemia | – | 3 | – | – |
| Hypermagnesemia | – | 11 | – | 13 |
| Hyponatremia | – | 3 | – | – |
| Hematologic | ||||
| Anemia | – | 14 | – | 8 |
| Lymphopenia | – | 15 | – | 15 |
| Neutropenia | – | 18 | – | 18 |
| Thrombocytopenia | – | 25 | – | 26 |
| Discontinuations | 60 | 76 | ||
| Due to AEs/toxicities | 22 | 24 | ||
| Due to disease progression | 18 | 20 | ||
Dashes indicate data not reported.
Data cutoff was 15 May 2013, with ≥48 months of follow-up from LSFV, except for cardiac and vascular events, which had a cutoff date of 23 May 2014, and an n = 284.
Data cutoff was 23 May 2014, with ≥48 months of follow-up from LSFV.
All-cause TEAEs were reported, regardless of relation to bosutinib treatment (includes unpublished data).
Individual hematologic TEAEs were clustered with the related terms from investigations.
Terms used to identify cardiac events excluded the HLGT pericardial disorders and included the HLGTs cardiac arrhythmias and heart failures and all subordinate terms under the SOC cardiac disorders; the PTs cardiac death, sudden cardiac death, and sudden death under the SOC general disorders and administration site conditions; and the PTs ejection fraction decreased, electrocardiogram QT interval abnormal, and electrocardiogram QT prolonged, and long QT syndrome congenital under the SOC in investigations.
Terms used to identify vascular events were the HLGTs coronary artery disorders, arteriosclerosis, stenosis, vascular insufficiency and necrosis, embolism and thrombosis, arterial therapeutic procedures (excluding aortic); the HLTs central nervous system hemorrhages and cerebrovascular accidents, central nervous system vascular disorders NEC, non-site specific vascular disorders NEC, peripheral vascular disorders NEC (excluding the PTs flushing and hot flash), transient cerebrovascular events, vascular imaging procedures NEC, and vascular therapeutic procedures NEC and all subordinate terms.
AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CP 2L, chronic phase, second-line treatment; CP 3L, chronic phase, third-line treatment; CP CML, chronic phase chronic myeloid leukemia; HLGT, high-level group term; HLT, high-level term; LSFV, last subject’s first visit; NEC, not elsewhere classified; PT, preferred term; SOC, system organ class; TEAE, treatment-emergent adverse event; TKI, tyrosine kinase inhibitor.