The main 1-year results of the company-sponsored trials that were considered for approval of 2GTKIs in the first-line setting by the FDA and the EMA
| . | ENESTnd . | DASISION . | BFORE . | |||
|---|---|---|---|---|---|---|
| Imatinib . | Nilotinib . | Imatinib . | Dasatinib . | Imatinib . | Bosutinib . | |
| Daily dose, mg | 400 × 1 | 300 × 2 | 400 × 1 | 100 × 1 | 400 × 1 | 400 × 1 |
| No. of patients | 282 | 283 | 259 | 260 | 246 | 246 |
| Median age, y | 46 | 47 | 49 | 46 | 53 | 52 |
| Low risk, % | 37* | 37* | 33† | 33† | 39* | 38* |
| Intermediate risk, % | 36* | 36* | 48† | 47† | 39* | 31* |
| High risk, % | 28* | 28* | 19† | 19† | 21* | 21* |
| CCyR, by 1 y | 69%; P < .001 | 80% | 72%; P < .001 | 83% | 66%; P < .007 | 77% |
| MMR, at/by 1 y | at 22%; P < .001 | 44% | by 28%; P < .001 | 46% | at 37%; P = .02 | 47% |
| D/C, in 5 y | 50% | 40% | 37% | 39% | ||
| MMR, by 5 y | 60%; P < .0001 | 77% | 66%; P = 0.0002 | 76% | ||
| MR 4.0, by 5 y | 42%; P < .0001 | 66% | NR | |||
| MR 4.5, by 5 y | 31%; P < .0001 | 54% | 33%; P = .02 | 42% | ||
| PFS, 5-y | 91% | 92% | 85% | 86% | ||
| OS, 5-y | 92% | 94% | 90% | 91% | ||
| LRD, 5-y | 6%; P = .02 | 2% | NR | |||
| . | ENESTnd . | DASISION . | BFORE . | |||
|---|---|---|---|---|---|---|
| Imatinib . | Nilotinib . | Imatinib . | Dasatinib . | Imatinib . | Bosutinib . | |
| Daily dose, mg | 400 × 1 | 300 × 2 | 400 × 1 | 100 × 1 | 400 × 1 | 400 × 1 |
| No. of patients | 282 | 283 | 259 | 260 | 246 | 246 |
| Median age, y | 46 | 47 | 49 | 46 | 53 | 52 |
| Low risk, % | 37* | 37* | 33† | 33† | 39* | 38* |
| Intermediate risk, % | 36* | 36* | 48† | 47† | 39* | 31* |
| High risk, % | 28* | 28* | 19† | 19† | 21* | 21* |
| CCyR, by 1 y | 69%; P < .001 | 80% | 72%; P < .001 | 83% | 66%; P < .007 | 77% |
| MMR, at/by 1 y | at 22%; P < .001 | 44% | by 28%; P < .001 | 46% | at 37%; P = .02 | 47% |
| D/C, in 5 y | 50% | 40% | 37% | 39% | ||
| MMR, by 5 y | 60%; P < .0001 | 77% | 66%; P = 0.0002 | 76% | ||
| MR 4.0, by 5 y | 42%; P < .0001 | 66% | NR | |||
| MR 4.5, by 5 y | 31%; P < .0001 | 54% | 33%; P = .02 | 42% | ||
| PFS, 5-y | 91% | 92% | 85% | 86% | ||
| OS, 5-y | 92% | 94% | 90% | 91% | ||
| LRD, 5-y | 6%; P = .02 | 2% | NR | |||
For ENESTnd11 and DASISION,12 also the follow-up results, at 5 years, are shown, confirming a higher rate and depth of molecular response, but showing no superiority in PFS and OS. From the ENESTnd study, a small but significant difference in leukemia-related deaths was also reported.
at, the proportion of patients with that response at 1 year; by, cumulative incidence of that response after 1 year or 5 years; CCyR, complete cytogenetic response (Ph+ 0); D/C, discontinued for ever the treatment assigned; EMA, European Medicine Agency; FDA, Federal Drug Administration; MMR, major molecular response (BCR-ABL1 ≤0.1%IS); MR 4.0, BCR-ABL1 ≤0.01%IS; MR 4.5, BCR-ABL1 ≤0.0032%IS; PFS, progression-free survival.
Sokal risk.
EURO risk.