Table 3. Data for QTc prolongation for TKIs.
| TKI | Studies | Increase of QT interval | Result absolute value | Conclusion |
|---|---|---|---|---|
| Imatinib | ENESTnd imatinib 400 mg (n=280)3 | >480 ms: 0.7% >500 ms: 0.4% | Symptomatic prolongation in 2.5% | |
| Nilotinib | 2101 CP and APa | >30 ms: 29.4% >60 ms: 1.3% | >450 ms: 10.2% >480 ms: 1.1% >500 ms: 0.5% | No episode of torsade de pointes |
| Nilotinib | ENESTnd, nilotinib 300 mg (n=279)3 | >480 or 500 ms: 0% | Symptomatic prolongation in 1.8% | |
| Bosutinib | Healthy adult subjects73 and BELA trial74 | No subjects had change from baseline >30 ms | No subjects had QTcB, QTcF, QTcI or QTcN >450 ms. | No clinically relevant PK/PD relationship was observed between bosutinib concentrations and QTc BELA: no data provided |
| Ponatinib | Phase 1 trial, AP24534-07-10175 | On 30 mg dosage: decrease of QT On 45 mg dosages: Increase of 3.3 ms | Low risk of QT prolongation | |
| Dasatinib | 2440 patientsa,76 | Maximum mean Changes in QTcF (90% upper bound CI) from baseline ranged from 7.0 to 13.4 ms. | >500 ms: 1% |
Abbreviations: AP, accelerated phase; CP, chronic phase.
a
Information taken from investigator brochure.