AREN0533
Treatment of Newly Diagnosed Higher Risk Favorable Histology Wilms Tumors
Phase 3N = 292NCT00379340
- Population
- Children with newly diagnosed stage IV favourable-histology Wilms tumour and lung metastases
- Design
- Children's Oncology Group non-randomised study of favourable-histology Wilms tumour with isolated lung metastases. Patients with a complete lung nodule response (CR) after 6 weeks of DD4A continued chemotherapy without lung radiotherapy; patients with incomplete response (IR) or loss of heterozygosity at chromosomes 1p/16q received lung radiotherapy and four cycles of cyclophosphamide/etoposide in addition to DD4A drugs (regimen M). Designed to preserve a 4-year EFS of 85% for CR and improve 4-year EFS from 75% to 85% for IR; 292 assessable patients (133 CR, 159 IR). Combined LOH 1p/16q, stage III-IV: regimen M with radiotherapy (51 enrolled in AREN0533 per the augmentation report). Registry record NCT00379340: actual enrolment 395.
- Arms
- Complete lung response: DD4A without lung radiotherapy (experimental): Continue DD4A chemotherapy without lung radiotherapy after complete lung nodule response at 6 weeks
- Incomplete lung response: regimen M with lung radiotherapy (experimental): Lung radiotherapy and four cycles of cyclophosphamide/etoposide in addition to DD4A drugs (regimen M)
- All assessable patients with lung metastases (experimental): Risk-stratified treatment: CR continues DD4A without lung radiotherapy; IR receives regimen M with lung radiotherapy
- NWTS-5 historical group (stage IV favourable histology with lung metastases) (control): Treatment given in NWTS-5 (historical comparison)
- Combined LOH 1p/16q, stage III-IV: regimen M with radiotherapy (experimental): Regimen M (vincristine, dactinomycin, doxorubicin alternating with cyclophosphamide and etoposide) and radiation therapy
- NWTS-5 historical group (combined LOH 1p/16q, stage III-IV) (control): Treatment given in NWTS-5 (updated 4-year EFS used as the comparison)
- People
- Dix DB, Children's Oncology Group
Δ 48-month EFS+12.9 pointsΔ 48-month OS+11.6 pointsΔ 48-month EFS+28.9 points
Show the numbers
| Endpoint | Analysis | Complete lung response: DD4A without lung radiotherapy / Incomplete lung response: regimen M with lung radiotherapy / All assessable patients with lung metastases / Combined LOH 1p/16q, stage III-IV: regimen M with radiotherapy | NWTS-5 historical group (stage IV favourable histology with lung metastases) / NWTS-5 historical group (combined LOH 1p/16q, stage III-IV) | Effect |
|---|---|---|---|---|
| EFSPatients with complete lung nodule response (133 assessable) | primaryDix 2018 | 79.5% at 4 y (71.2–87.8%) | — | P=.052P is for expected versus observed event rates (15% expected and 20.2% observed), as printed; the design aimed to preserve 4-year EFS of 85%. |
| OSPatients with complete lung nodule response (133 assessable) | primaryDix 2018 | 96.1% at 4 y (92.1–100.0%) | — | — |
| EFSPatients with incomplete lung nodule response (159 assessable) | primaryDix 2018 | 88.5% at 4 y (81.8–95.3%) | — | P<.001P is for expected versus observed event rates (25% expected and 12.2% observed), as printed; the design aimed to improve 4-year EFS from 75% to 85%. |
| OSPatients with incomplete lung nodule response (159 assessable) | primaryDix 2018 | 95.4% at 4 y (90.9–99.8%) | — | — |
| EFSAll 292 assessable patients, compared with the predecessor NWTS-5 study | primaryDix 2018 | 85.4% at 4 y (80.5–90.2%) | 72.5% at 4 y (66.9–78.1%) | P<.001Historical (non-randomised) comparison with NWTS-5. |
| OSAll 292 assessable patients, compared with the predecessor NWTS-5 study | primaryDix 2018 | 95.6% at 4 y (92.8–98.4%) | 84% at 4 y (79.4–88.6%) | P<.001Historical (non-randomised) comparison with NWTS-5. |
| EFSEligible patients with stage III-IV favourable-histology Wilms tumour and combined LOH 1p/16q (51 enrolled in AREN0533) | primarymedian follow-up 5.73 yearsDix 2019 | 90.2% at 4 y (81.8–98.6%) | 61.3% at 4 y | P=.001Historical comparison with the NWTS-5 updated 4-year EFS; log-rank test per the abstract. Median follow-up 5.73 years is for the 83 eligible patients in AREN0532 and AREN0533 together. Grade 3 or higher febrile neutropenia 39.2% and infections 21.6% with regimen M. |
| Endpoint | Analysis | Complete lung response: DD4A without lung radiotherapy / Incomplete lung response: regimen M with lung radiotherapy / All assessable patients with lung metastases / Combined LOH 1p/16q, stage III-IV: regimen M with radiotherapy | NWTS-5 historical group (stage IV favourable histology with lung metastases) / NWTS-5 historical group (combined LOH 1p/16q, stage III-IV) | Effect |
|---|---|---|---|---|
| EFSPatients with complete lung nodule response (133 assessable) | primaryDix 2018 | 79.5% at 4 y (71.2–87.8%) | — | P=.052P is for expected versus observed event rates (15% expected and 20.2% observed), as printed; the design aimed to preserve 4-year EFS of 85%. |
| OSPatients with complete lung nodule response (133 assessable) | primaryDix 2018 | 96.1% at 4 y (92.1–100.0%) | — | — |
| EFSPatients with incomplete lung nodule response (159 assessable) | primaryDix 2018 | 88.5% at 4 y (81.8–95.3%) | — | P<.001P is for expected versus observed event rates (25% expected and 12.2% observed), as printed; the design aimed to improve 4-year EFS from 75% to 85%. |
| OSPatients with incomplete lung nodule response (159 assessable) | primaryDix 2018 | 95.4% at 4 y (90.9–99.8%) | — | — |
| EFSAll 292 assessable patients, compared with the predecessor NWTS-5 study | primaryDix 2018 | 85.4% at 4 y (80.5–90.2%) | 72.5% at 4 y (66.9–78.1%) | P<.001Historical (non-randomised) comparison with NWTS-5. |
| OSAll 292 assessable patients, compared with the predecessor NWTS-5 study | primaryDix 2018 | 95.6% at 4 y (92.8–98.4%) | 84% at 4 y (79.4–88.6%) | P<.001Historical (non-randomised) comparison with NWTS-5. |
| EFSEligible patients with stage III-IV favourable-histology Wilms tumour and combined LOH 1p/16q (51 enrolled in AREN0533) | primarymedian follow-up 5.73 yearsDix 2019 | 90.2% at 4 y (81.8–98.6%) | 61.3% at 4 y | P=.001Historical comparison with the NWTS-5 updated 4-year EFS; log-rank test per the abstract. Median follow-up 5.73 years is for the 83 eligible patients in AREN0532 and AREN0533 together. Grade 3 or higher febrile neutropenia 39.2% and infections 21.6% with regimen M. |
Appears in
Sources
Dix DB, Seibel NL, Chi YY, Khanna G, Gratias E, Anderson JR, et al. Treatment of Stage IV Favorable Histology Wilms Tumor With Lung Metastases: A Report From the Children's Oncology Group AREN0533 Study. J Clin Oncol. 2018;36(16):1564-1570.
Dix DB, Fernandez CV, Chi YY, Mullen EA, Geller JI, Gratias EJ, et al. Augmentation of Therapy for Combined Loss of Heterozygosity 1p and 16q in Favorable Histology Wilms Tumor: A Children's Oncology Group AREN0532 and AREN0533 Study Report. J Clin Oncol. 2019;37(30):2769-2777.