Table 1. Summary of major TKI trials.
| Phase III trial | IRIS 12 | DASISION 32 | ENEST 26 | BELA 35 | ||||||||
| Study design | ||||||||||||
| Number of study arms |
Two | Two | Three: Imatinib 400 mg OD/ Nilotinib 300mg/400mg BID¥ |
Two | ||||||||
| Crossover | Allowed if treatment failure or intolerance |
No | No | No | ||||||||
| Dose modification |
Dose escalation allowed | Interruptions, dose reductions or escalations allowed |
Allowed escalation in Imatinib dose; not Nilotinib |
Allowed escalation for both Bosutinib and Imatinib |
||||||||
| Total number of patients |
1106 | 519 | 846 | 502 | ||||||||
|
Interferon
+low dose cytarabine |
Imatinib |
P-
value |
Dasatinib | Imatinib |
P-
value |
Nilotinib | Imatinib |
P-
value |
Bosutinib | Imatinib |
P-
value |
|
| Study dosage | Interferon: max tolerated. Cytarabine: 20 mg/m2 |
400 mg daily |
100 mg daily |
400 mg daily |
300 mg BID¥ |
400 mg daily |
500 mg daily |
400 mg daily |
||||
|
Follow-up at
initial analysis |
12 mo | 12 mo | 12 mo | 12 mo | ||||||||
| CHR | 56% | 95% | <.001 | NA | NA | 71% | 85% | NS | ||||
| CCR | 9% | 74% | <.001 | 83% | 72% | 0.001 | 80% | 65% | <.001 | 70% | 68% | NS |
| MMR | NA | 39% | 46% | 28% | <.001 | 44% | 22% | <.001 | 41% | 27% | <.001 | |
| Median time to first CHR |
2.5 mo | 1 mo | NA | NA | NA | NA | 4.4 wk | 4.6 wk | NS | |||
| Median time to first CCR |
NA | NA | NA | NA | NA | NA | 12.9 wk | 24.6 wk | <.001 | |||
| Median time to first MMR |
NA | NA | HR 2.0 | <.001 | 8.6 mo | NA | 37.1 wk | 72.3 wk | <.001 | |||
| Progression to AP/BP |
7% | 1% | <.001 | 2% | 4% | <1% | 4% | 0.01 | 2% | 4% | ||
| Event free survival |
NA | NA | NA | NA | NA | NA | 94% | 93% | ||||
| Progression free survival |
80% | 97% | <.001 | 96% | 97% | NS | NA | NA | NA | NA | ||
| Overall survival |
95%* | 97%* | NS* | 97% | 99% | NS | NA | NA | 99% | 97% | ||
|
Follow-up
last reported |
8 year 17 | 5 year 49 | 5 year 27,28 | 2 year 50 | ||||||||
| Patients on study |
NA | 55% | 61% | 63% | 60% | 50% | 63% | 71% | ||||
| CCR | NA | NA | 83% | 78% | NS | NA | NA | 58% | 65% | NS | ||
| MMR | NA | 86% | 76% | 64% | .002 | 77% | 60% | <.001 | 47% | 41% | NS | |
| MR4.5 | NA | NA | 42% | 33% | 0.025 | 54% | 31% | <.001 | NA | NA | ||
| Progression to AP/BP |
NA | 8% | 5% | 7% | 4% | 8% | 0.04 | 2% | 5% | 0.019 | ||
| Event free survival |
NA | 81% | NA | NA | NA | NA | 92% | 88% | ||||
| Progression free survival |
NA | NA | 85% | 86% | NS | NA | NA | NA | NA | |||
| Overall survival |
NA | 85% | 91% | 90% | NS | 94% | 92% | NS | 97% | 95% | ||
Abbreviations: CHR: Complete hematologic response; CCR: Complete cytogenetic response; MMR: Major molecular response BCR-ABL1 PCR ≤ 0.01% on International Scale; MR4.5: BCR-ABL1 PCR ≤ 0.0032% on International Scale; AP: Accelerated phase; BP: Blast phase; NA: Not available; NS: Not significant;
*
at 18 months.
¥
there was no significant difference in results between the two Nilotinib arms so we include the more commonly used dose of 300mg BID in this table.