AREN0532
Treatment for Very Low and Standard Risk Favorable Histology Wilms Tumor
Phase 3N = 116NCT00352534
- Population
- Children with newly diagnosed stage I-III favourable-histology Wilms tumour enrolled through the AREN03B2 biology study
- Design
- Children's Oncology Group non-randomised study with central review of pathology, imaging and surgical reports. Very low-risk Wilms tumour (stage I favourable histology, nephrectomy weight under 550 g, age under 2 years): nephrectomy then follow-up without adjuvant chemotherapy; 116 eligible patients; powered to detect a reduction in 4-year EFS from 87% to 75% and OS from 95% to 88%. Stage III favourable histology: regimen DD4A (vincristine, dactinomycin, doxorubicin) plus radiotherapy; 588 prospectively treated patients October 2006 to August 2013; 535 studied after exclusion of 5 ineligible patients and 40 with combined LOH 1p/16q (the abstract also excludes 8 with anaplasia on delayed-nephrectomy histology from the survival analysis). Combined LOH 1p/16q, stage I-II: DD4A without radiotherapy (32 enrolled in AREN0532 per the augmentation report). Registry record NCT00352534: actual enrolment 808.
- Arms
- Nephrectomy only (very low-risk) (experimental): Nephrectomy then follow-up without adjuvant chemotherapy
- DD4A plus radiotherapy (stage III) (experimental): Regimen DD4A (vincristine, dactinomycin, doxorubicin) and radiation therapy
- DD4A without radiotherapy (combined LOH 1p/16q, stage I-II) (experimental): Regimen DD4A (vincristine, dactinomycin, doxorubicin) without radiation therapy
- NWTS-5 historical group (combined LOH 1p/16q, stage I-II) (control): Treatment given in NWTS-5 (updated 4-year EFS used as the comparison)
- People
- Fernandez CV, Children's Oncology Group
Δ 48-month EFS+18.5 points
Show the numbers
| Endpoint | Analysis | Nephrectomy only (very low-risk) / DD4A plus radiotherapy (stage III) / DD4A without radiotherapy (combined LOH 1p/16q, stage I-II) | NWTS-5 historical group (combined LOH 1p/16q, stage I-II) | Effect |
|---|---|---|---|---|
| EFSEligible very low-risk patients (116) managed with nephrectomy only | primarymedian follow-up 80 monthsFernandez 2017 | 89.7% at 4 y (84.1–95.2%) | — | Twelve patients relapsed. Median follow-up 80 months (range 5 to 97). |
| OSEligible very low-risk patients (116) managed with nephrectomy only | primarymedian follow-up 80 monthsFernandez 2017 | 100% at 4 y | — | The abstract prints overall survival as 100% without a confidence interval. |
| EFS535 patients with stage III favourable-histology Wilms tumour without combined LOH 1p/16q, treated with DD4A and radiotherapy | primarymedian follow-up 5.2 yearsFernandez 2018 | 88% at 4 y (85–91%) | — | Median follow-up 5.2 years (range 0.2 to 9.5). 58 of 66 relapses occurred in the first 2 years. |
| OS535 patients with stage III favourable-histology Wilms tumour without combined LOH 1p/16q, treated with DD4A and radiotherapy | primarymedian follow-up 5.2 yearsFernandez 2018 | 97% at 4 y (95–99%) | — | — |
| EFSEligible patients with stage I-II favourable-histology Wilms tumour and combined LOH 1p/16q (32 enrolled in AREN0532) | primarymedian follow-up 5.73 yearsDix 2019 | 87.3% at 4 y (75.1–99.5%) | 68.8% at 4 y | P=.042Historical comparison with the NWTS-5 updated 4-year EFS; log-rank test per the abstract. Median follow-up 5.73 years (range 2.84 to 9.63) is for the 83 eligible patients in AREN0532 and AREN0533 together. |
| Endpoint | Analysis | Nephrectomy only (very low-risk) / DD4A plus radiotherapy (stage III) / DD4A without radiotherapy (combined LOH 1p/16q, stage I-II) | NWTS-5 historical group (combined LOH 1p/16q, stage I-II) | Effect |
|---|---|---|---|---|
| EFSEligible very low-risk patients (116) managed with nephrectomy only | primarymedian follow-up 80 monthsFernandez 2017 | 89.7% at 4 y (84.1–95.2%) | — | Twelve patients relapsed. Median follow-up 80 months (range 5 to 97). |
| OSEligible very low-risk patients (116) managed with nephrectomy only | primarymedian follow-up 80 monthsFernandez 2017 | 100% at 4 y | — | The abstract prints overall survival as 100% without a confidence interval. |
| EFS535 patients with stage III favourable-histology Wilms tumour without combined LOH 1p/16q, treated with DD4A and radiotherapy | primarymedian follow-up 5.2 yearsFernandez 2018 | 88% at 4 y (85–91%) | — | Median follow-up 5.2 years (range 0.2 to 9.5). 58 of 66 relapses occurred in the first 2 years. |
| OS535 patients with stage III favourable-histology Wilms tumour without combined LOH 1p/16q, treated with DD4A and radiotherapy | primarymedian follow-up 5.2 yearsFernandez 2018 | 97% at 4 y (95–99%) | — | — |
| EFSEligible patients with stage I-II favourable-histology Wilms tumour and combined LOH 1p/16q (32 enrolled in AREN0532) | primarymedian follow-up 5.73 yearsDix 2019 | 87.3% at 4 y (75.1–99.5%) | 68.8% at 4 y | P=.042Historical comparison with the NWTS-5 updated 4-year EFS; log-rank test per the abstract. Median follow-up 5.73 years (range 2.84 to 9.63) is for the 83 eligible patients in AREN0532 and AREN0533 together. |
Appears in
Sources
Fernandez CV, Perlman EJ, Mullen EA, Chi YY, Hamilton TE, Gow KW, et al. Clinical Outcome and Biological Predictors of Relapse After Nephrectomy Only for Very Low-risk Wilms Tumor: A Report From Children's Oncology Group AREN0532. Ann Surg. 2017;265(4):835-840.
Fernandez CV, Mullen EA, Chi YY, Ehrlich PF, Perlman EJ, Kalapurakal JA, et al. Outcome and Prognostic Factors in Stage III Favorable-Histology Wilms Tumor: A Report From the Children's Oncology Group Study AREN0532. J Clin Oncol. 2018;36(3):254-261.
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.