NMTRC003B
A Phase II Preventative Trial of DFMO (Eflornithine HCl) as a Single Agent in Patients With High Risk Neuroblastoma in Remission
Phase 2N = 141NCT02395666
- Population
- Patients with high-risk neuroblastoma in remission after standard up-front therapy (stratum 1) or after salvage therapy for relapsed or refractory disease (stratum 2). The external control comprised ANBL0032 patients who had been treated with dinutuximab and could have been eligible for NMTRC003B.
- Design
- Single-arm phase 2 trial (NMTRC003B and an identically designed predecessor trial, 2012 to 2016) of oral eflornithine (DFMO) for up to 2 years after remission; reported in 2018 with intention-to-treat EFS and OS, and in 2024 compared with patient-level data from the COG ANBL0032 trial as an external control (overall and propensity score-matched analyses).
- Primary endpoint
- EFS
- Arms
- DFMO, stratum 1 (experimental, n = 100): Oral eflornithine (DFMO) 750 ± 250 mg/m2 twice daily for up to 2 years after standard up-front therapy
- DFMO, stratum 2 (experimental, n = 39): Oral eflornithine (DFMO) 750 ± 250 mg/m2 twice daily for up to 2 years after salvage therapy for relapsed or refractory disease
- DFMO-treated group (external-control analysis) (experimental, n = 92): NMTRC003B patients who took part in, or received up-front treatment consistent with, ANBL0032, treated with oral DFMO for up to 2 years
- External control (ANBL0032, no DFMO) (control, n = 852): ANBL0032 patients treated with dinutuximab-based immunotherapy who could have been eligible for NMTRC003B but did not enrol
- People
- Oesterheld J, senior author Saulnier Sholler GL
EFSHR 0.50 (95% CI 0.29–0.84)OSHR 0.38 (95% CI 0.19–0.76)EFSHR 0.48 (95% CI 0.27–0.85)Δ 48-month EFS+11 pointsOSHR 0.32 (95% CI 0.15–0.70)Δ 48-month OS+12 points
Show the numbers
| Endpoint | Analysis | DFMO, stratum 1 / DFMO, stratum 2 / DFMO-treated group (external-control analysis) | External control (ANBL0032, no DFMO) | Effect |
|---|---|---|---|---|
| EFSStratum 1, intention-to-treat (100 eligible of 101 enrolled)Event-free survival from first dose of DFMO | primarySholler 2018 | 84% at 2 y | — | Reported as 84% (± 4%); the ± is a standard error, not a confidence interval. Single arm, no comparator in this report. |
| OSStratum 1, intention-to-treat (100 eligible of 101 enrolled) | primarySholler 2018 | 97% at 2 y | — | Reported as 97% (± 2%); the ± is a standard error. Single arm. |
| OSStratum 2 (39 enrolled) | primarySholler 2018 | 84% at 2 y | — | Reported as 84% (± 6%); the ± is a standard error. Single arm. |
| EFSDFMO-treated group (n = 92) vs ANBL0032 external control (n = 852), unmatchedEvent-free survival (relapse, progression, secondary malignancy or death from any cause), measured from the end of immunotherapy | exploratorymedian follow-up 6.1 yearsOesterheld 2024 | — | — | HR 0.50 (95% CI 0.29–0.84)P=0.008Hazard ratio for DFMO vs no DFMO as reported. External-control (non-randomised) analysis. Median follow-up 6.1 years (IQR 5.2 to 7.2) in the DFMO group and 5.0 years (IQR 3.5 to 7.0) in the control group. Four-year EFS in the full text: 84% vs 72%. |
| OSDFMO-treated group (n = 92) vs ANBL0032 external control (n = 852), unmatchedOverall survival, measured from the end of immunotherapy | exploratoryOesterheld 2024 | — | — | HR 0.38 (95% CI 0.19–0.76)P=0.007Hazard ratio for DFMO vs no DFMO as reported. External-control (non-randomised) analysis. Four-year OS in the full text: 96% vs 84%. |
| EFS3:1 propensity score-matched cohorts: 90 DFMO-treated vs 270 ANBL0032 controlsEvent-free survival (relapse, progression, secondary malignancy or death from any cause), measured from the end of immunotherapy | exploratoryOesterheld 2024 | 84% at 4 y | 73% at 4 y | HR 0.48 (95% CI 0.27–0.85)P=0.01Matched on 11 baseline characteristics with exact matching on MYCN; unadjusted Cox model. One DFMO patient fell outside the overlapping propensity range. The FDA announcement reports the same hazard ratio for its primary analysis of 90 vs 270 patients. |
| OS3:1 propensity score-matched cohorts: 90 DFMO-treated vs 270 ANBL0032 controlsOverall survival, measured from the end of immunotherapy | exploratoryOesterheld 2024 | 96% at 4 y | 84% at 4 y | HR 0.32 (95% CI 0.15–0.70)P=0.005Matched analysis as above. The FDA announcement reports the same hazard ratio. |
| Endpoint | Analysis | DFMO, stratum 1 / DFMO, stratum 2 / DFMO-treated group (external-control analysis) | External control (ANBL0032, no DFMO) | Effect |
|---|---|---|---|---|
| EFSStratum 1, intention-to-treat (100 eligible of 101 enrolled)Event-free survival from first dose of DFMO | primarySholler 2018 | 84% at 2 y | — | Reported as 84% (± 4%); the ± is a standard error, not a confidence interval. Single arm, no comparator in this report. |
| OSStratum 1, intention-to-treat (100 eligible of 101 enrolled) | primarySholler 2018 | 97% at 2 y | — | Reported as 97% (± 2%); the ± is a standard error. Single arm. |
| OSStratum 2 (39 enrolled) | primarySholler 2018 | 84% at 2 y | — | Reported as 84% (± 6%); the ± is a standard error. Single arm. |
| EFSDFMO-treated group (n = 92) vs ANBL0032 external control (n = 852), unmatchedEvent-free survival (relapse, progression, secondary malignancy or death from any cause), measured from the end of immunotherapy | exploratorymedian follow-up 6.1 yearsOesterheld 2024 | — | — | HR 0.50 (95% CI 0.29–0.84)P=0.008Hazard ratio for DFMO vs no DFMO as reported. External-control (non-randomised) analysis. Median follow-up 6.1 years (IQR 5.2 to 7.2) in the DFMO group and 5.0 years (IQR 3.5 to 7.0) in the control group. Four-year EFS in the full text: 84% vs 72%. |
| OSDFMO-treated group (n = 92) vs ANBL0032 external control (n = 852), unmatchedOverall survival, measured from the end of immunotherapy | exploratoryOesterheld 2024 | — | — | HR 0.38 (95% CI 0.19–0.76)P=0.007Hazard ratio for DFMO vs no DFMO as reported. External-control (non-randomised) analysis. Four-year OS in the full text: 96% vs 84%. |
| EFS3:1 propensity score-matched cohorts: 90 DFMO-treated vs 270 ANBL0032 controlsEvent-free survival (relapse, progression, secondary malignancy or death from any cause), measured from the end of immunotherapy | exploratoryOesterheld 2024 | 84% at 4 y | 73% at 4 y | HR 0.48 (95% CI 0.27–0.85)P=0.01Matched on 11 baseline characteristics with exact matching on MYCN; unadjusted Cox model. One DFMO patient fell outside the overlapping propensity range. The FDA announcement reports the same hazard ratio for its primary analysis of 90 vs 270 patients. |
| OS3:1 propensity score-matched cohorts: 90 DFMO-treated vs 270 ANBL0032 controlsOverall survival, measured from the end of immunotherapy | exploratoryOesterheld 2024 | 96% at 4 y | 84% at 4 y | HR 0.32 (95% CI 0.15–0.70)P=0.005Matched analysis as above. The FDA announcement reports the same hazard ratio. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| EFS | 0.5 | 0.29–0.84 |
| OS | 0.38 | 0.19–0.76 |
| EFS | 0.48 | 0.27–0.85 |
| OS | 0.32 | 0.15–0.7 |
Appears in
Sources
Oesterheld J, Ferguson W, Kraveka JM, Bergendahl G, Clinch T, Lorenzi E, et al. Eflornithine as Postimmunotherapy Maintenance in High-Risk Neuroblastoma: Externally Controlled, Propensity Score-Matched Survival Outcome Comparisons. J Clin Oncol. 2024;42(1):90-102.
Sholler GLS, Ferguson W, Bergendahl G, Bond JP, Neville K, Eslin D, et al. Maintenance DFMO Increases Survival in High Risk Neuroblastoma. Sci Rep. 2018;8(1):14445.