APL0406
A Randomised Phase III Study to Compare Arsenic Trioxide (ATO) Combined to ATRA Versus Standard ATRA and Anthracycline-Based Chemotherapy (AIDA Regimen) for Newly Diagnosed, Non High-Risk Acute Promyelocytic Leukemia
Phase 3N = 276NCT00482833
- Population
- Adults aged 18 to 71 years with newly diagnosed low- or intermediate-risk APL (white-cell count at diagnosis ≤10 × 10^9 per liter)
- Design
- Prospective, randomized, multicenter, open-label noninferiority trial. The primary report was designed to show that the difference in 2-year event-free survival between groups was not greater than 5%. ATRA-chemotherapy arm: ATRA-idarubicin induction, three consolidation cycles with ATRA plus chemotherapy, then maintenance with low-dose chemotherapy and ATRA.
- Primary endpoint
- EFS
- Arms
- ATRA plus arsenic trioxide (experimental): ATRA plus arsenic trioxide for induction and consolidation
- ATRA plus chemotherapy (control): ATRA-idarubicin induction, three consolidation cycles of ATRA plus chemotherapy, maintenance with low-dose chemotherapy and ATRA
- People
- Lo-Coco F, Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA); the Italian-German APL0406 trial
Δ Complete remission rate+5 pointsΔ 24-month EFS+11 pointsΔ Complete remission rate+3 pointsΔ 50-month EFS+17.3 pointsΔ 50-month Cumulative incidence of relapse−12 pointsΔ 50-month OS+6.6 points
Show the numbers
| Endpoint | Analysis | ATRA plus arsenic trioxide | ATRA plus chemotherapy | Effect |
|---|---|---|---|---|
| Complete remission ratePatients evaluable for response: 77 (ATRA-arsenic trioxide) and 79 (ATRA-chemotherapy) | primaryLo-Coco 2013 | 100% | 95% | P=0.1277 of 77 versus 75 of 79 evaluable patients. The median follow-up of 34.4 months in the abstract applies to the survival analyses, not to this response rate. |
| EFSNot stated in the abstract (the abstract's complete-remission analysis covers 77 and 79 evaluable patients) | primarymedian follow-up 34.4 monthsLo-Coco 2013 | 97% at 2 y | 86% at 2 y | P<0.001 for noninferiority; 0.02 for superiority95% confidence interval for the difference in 2-year EFS: 2 to 22 percentage points. Overall survival was also reported as better with ATRA-arsenic trioxide (P=0.02); the abstract gives no overall survival values. Hematologic toxicity and infections were less frequent, and hepatic toxicity more frequent, with ATRA-arsenic trioxide. |
| Complete remission ratePatients evaluable for response to induction: 263 (127 ATRA-arsenic trioxide, 136 ATRA-chemotherapy) | finalPlatzbecker 2017 | 100% | 97% | P=0.12127 of 127 versus 132 of 136 patients. |
| EFSComplete series of enrolled patients (276 randomized); the abstract does not label the analysis population | finalmedian follow-up 40.6 monthsPlatzbecker 2017 | 97.3% at 50 mo | 80% at 50 mo | P<0.001 |
| Cumulative incidence of relapseComplete series of enrolled patients (276 randomized); the abstract does not label the analysis population | finalmedian follow-up 40.6 monthsPlatzbecker 2017 | 1.9% at 50 mo | 13.9% at 50 mo | P=0.0013Postinduction events in the abstract: two relapses and one death in complete remission with ATRA-arsenic trioxide; two instances of molecular resistance after the third consolidation, 15 relapses and five deaths in complete remission with ATRA-chemotherapy. |
| OSComplete series of enrolled patients (276 randomized); the abstract does not label the analysis population | finalmedian follow-up 40.6 monthsPlatzbecker 2017 | 99.2% at 50 mo | 92.6% at 50 mo | P=0.0073 |
| Endpoint | Analysis | ATRA plus arsenic trioxide | ATRA plus chemotherapy | Effect |
|---|---|---|---|---|
| Complete remission ratePatients evaluable for response: 77 (ATRA-arsenic trioxide) and 79 (ATRA-chemotherapy) | primaryLo-Coco 2013 | 100% | 95% | P=0.1277 of 77 versus 75 of 79 evaluable patients. The median follow-up of 34.4 months in the abstract applies to the survival analyses, not to this response rate. |
| EFSNot stated in the abstract (the abstract's complete-remission analysis covers 77 and 79 evaluable patients) | primarymedian follow-up 34.4 monthsLo-Coco 2013 | 97% at 2 y | 86% at 2 y | P<0.001 for noninferiority; 0.02 for superiority95% confidence interval for the difference in 2-year EFS: 2 to 22 percentage points. Overall survival was also reported as better with ATRA-arsenic trioxide (P=0.02); the abstract gives no overall survival values. Hematologic toxicity and infections were less frequent, and hepatic toxicity more frequent, with ATRA-arsenic trioxide. |
| Complete remission ratePatients evaluable for response to induction: 263 (127 ATRA-arsenic trioxide, 136 ATRA-chemotherapy) | finalPlatzbecker 2017 | 100% | 97% | P=0.12127 of 127 versus 132 of 136 patients. |
| EFSComplete series of enrolled patients (276 randomized); the abstract does not label the analysis population | finalmedian follow-up 40.6 monthsPlatzbecker 2017 | 97.3% at 50 mo | 80% at 50 mo | P<0.001 |
| Cumulative incidence of relapseComplete series of enrolled patients (276 randomized); the abstract does not label the analysis population | finalmedian follow-up 40.6 monthsPlatzbecker 2017 | 1.9% at 50 mo | 13.9% at 50 mo | P=0.0013Postinduction events in the abstract: two relapses and one death in complete remission with ATRA-arsenic trioxide; two instances of molecular resistance after the third consolidation, 15 relapses and five deaths in complete remission with ATRA-chemotherapy. |
| OSComplete series of enrolled patients (276 randomized); the abstract does not label the analysis population | finalmedian follow-up 40.6 monthsPlatzbecker 2017 | 99.2% at 50 mo | 92.6% at 50 mo | P=0.0073 |
Appears in
Sources
Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013;369(2):111-21.
Platzbecker U, Avvisati G, Cicconi L, Thiede C, Paoloni F, Vignetti M, et al. Improved Outcomes With Retinoic Acid and Arsenic Trioxide Compared With Retinoic Acid and Chemotherapy in Non-High-Risk Acute Promyelocytic Leukemia: Final Results of the Randomized Italian-German APL0406 Trial. J Clin Oncol. 2017;35(6):605-612.