ENESTnd
Needs reviewNilotinib versus imatinib for newly diagnosed chronic myeloid leukemia
Phase 3N = 846NCT00471497
- Population
- Newly diagnosed Philadelphia chromosome-positive CML in chronic phase
- Design
- Randomized, open-label, multicenter phase 3 study; 1:1:1 assignment to nilotinib 300 mg twice daily, nilotinib 400 mg twice daily or imatinib 400 mg once daily.
- Primary endpoint
- MMR
- Arms
- Nilotinib 300 mg twice daily (experimental, n = 282): Nilotinib 300 mg twice daily
- Nilotinib 400 mg twice daily (experimental, n = 281): Nilotinib 400 mg twice daily
- Imatinib (control, n = 283): Imatinib 400 mg once daily
- People
- Saglio G, ENESTnd Investigators
Δ MMR+22 pointsΔ CCyR+15 pointsΔ 60-month MR4.5+23 pointsΔ 120-month MMR+15.2 pointsΔ 120-month MR4.5+21.8 pointsΔ 120-month OS−0.7 points
Show the numbers
| Endpoint | Analysis | Nilotinib 300 mg twice daily / Nilotinib 400 mg twice daily | Imatinib | Effect |
|---|---|---|---|---|
| MMRRandomly assigned patients (analysis population not stated in the abstract)Major molecular response at 12 months (primary endpoint) | primarySaglio 2010 | 44% | 22% | P<0.001P<0.001 for each nilotinib dose versus imatinib. |
| CCyRRandomly assigned patients (analysis population not stated in the abstract)Complete cytogenetic response by 12 months | primarySaglio 2010 | 80% | 65% | P<0.001P<0.001 for each nilotinib dose versus imatinib. |
| MR4.5Intent-to-treat (all randomized patients), per the 5-year reportMolecular response 4.5 (BCR-ABL ≤0.0032% on the International Scale) achieved by 5 years, a cumulative rate (patients who achieved the response at or before each time point were counted as responders) | long term-updateHochhaus 2016 | 54% at 5 y | 31% at 5 y | Minimum follow-up of 5 years. |
| MMRIntent-to-treat (all randomized patients; N=846)Cumulative 10-year rate of major molecular response | long term-updateKantarjian 2021 | 77.7% at 10 y | 62.5% at 10 y | At least 10 years of follow-up. |
| MR4.5Intent-to-treat (all randomized patients; N=846)Cumulative 10-year rate of molecular response 4.5 | long term-updateKantarjian 2021 | 61% at 10 y | 39.2% at 10 y | At least 10 years of follow-up. |
| OSIntent-to-treat (all randomized patients; N=846)Estimated 10-year overall survival | long term-updateKantarjian 2021 | 87.6% at 10 y | 88.3% at 10 y | Arm order (nilotinib 300 mg twice daily, nilotinib 400 mg twice daily, imatinib) confirmed in the full-text Table 2: 87.6% (95% CI 83.5 to 91.7), 90.3% (86.5 to 94.1), 88.3% (84.2 to 92.4); hazard ratio versus imatinib 1.07 (0.64 to 1.76), P=0.80 for 300 mg and 0.79 (0.46 to 1.36), P=0.40 for 400 mg, neither significant. |
| Endpoint | Analysis | Nilotinib 300 mg twice daily / Nilotinib 400 mg twice daily | Imatinib | Effect |
|---|---|---|---|---|
| MMRRandomly assigned patients (analysis population not stated in the abstract)Major molecular response at 12 months (primary endpoint) | primarySaglio 2010 | 44% | 22% | P<0.001P<0.001 for each nilotinib dose versus imatinib. |
| CCyRRandomly assigned patients (analysis population not stated in the abstract)Complete cytogenetic response by 12 months | primarySaglio 2010 | 80% | 65% | P<0.001P<0.001 for each nilotinib dose versus imatinib. |
| MR4.5Intent-to-treat (all randomized patients), per the 5-year reportMolecular response 4.5 (BCR-ABL ≤0.0032% on the International Scale) achieved by 5 years, a cumulative rate (patients who achieved the response at or before each time point were counted as responders) | long term-updateHochhaus 2016 | 54% at 5 y | 31% at 5 y | Minimum follow-up of 5 years. |
| MMRIntent-to-treat (all randomized patients; N=846)Cumulative 10-year rate of major molecular response | long term-updateKantarjian 2021 | 77.7% at 10 y | 62.5% at 10 y | At least 10 years of follow-up. |
| MR4.5Intent-to-treat (all randomized patients; N=846)Cumulative 10-year rate of molecular response 4.5 | long term-updateKantarjian 2021 | 61% at 10 y | 39.2% at 10 y | At least 10 years of follow-up. |
| OSIntent-to-treat (all randomized patients; N=846)Estimated 10-year overall survival | long term-updateKantarjian 2021 | 87.6% at 10 y | 88.3% at 10 y | Arm order (nilotinib 300 mg twice daily, nilotinib 400 mg twice daily, imatinib) confirmed in the full-text Table 2: 87.6% (95% CI 83.5 to 91.7), 90.3% (86.5 to 94.1), 88.3% (84.2 to 92.4); hazard ratio versus imatinib 1.07 (0.64 to 1.76), P=0.80 for 300 mg and 0.79 (0.46 to 1.36), P=0.40 for 400 mg, neither significant. |
Appears in
Sources
Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362(24):2251-9.
Hochhaus A, Saglio G, Hughes TP, Larson RA, Kim DW, Issaragrisil S, et al. Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. Leukemia. 2016;30(5):1044-54.
Kantarjian HM, Hughes TP, Larson RA, Kim DW, Issaragrisil S, le Coutre P, et al. Long-term outcomes with frontline nilotinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase: ENESTnd 10-year analysis. Leukemia. 2021;35(2):440-453.