COG AREN0533
A risk-adapted Wilms tumour trial: children whose lung metastases vanished after six weeks of chemotherapy were spared lung radiation, while those with stubborn nodules or a high-risk chromosome pattern got stronger chemotherapy and did better than in the past.
Overview
Single-arm, biology- and response-adapted phase 3 (Dix et al., JCO 2018 and 2019). Among 292 assessable patients with lung metastases, 133 had complete lung nodule response after six weeks of vincristine, dactinomycin and doxorubicin (DD4A) and continued without lung radiotherapy: 4-year EFS 79.5% with excellent overall survival, though events exceeded expectation. The 159 with incomplete response, or LOH at 1p/16q, received lung radiotherapy plus four cycles of cyclophosphamide and etoposide (Regimen M): 4-year EFS 88.5%, better than the 75% target. Overall 4-year EFS and OS were 85.4% and 95.6% versus 72.5% and 84.0% in the predecessor NWTS-5. Companion analysis of patients with 1p/16q LOH showed 4-year EFS of 87.3% (stage I-II, AREN0532) and 90.2% (stage III-IV, AREN0533), improved from 68.8% and 61.3% in NWTS-5. Together with AREN0532, it made molecular and response-based risk stratification the North American Wilms standard, mirroring the SIOP approach in Europe.
- 85.4 vs 72.5 out of 100 free of a major event at 4 years with AREN0533 risk-adapted compared with NWTS-5 (historical); 12.9 more per 100.
- Roughly one extra person helped for every 8 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- The p-value (<0.001) says a difference this large would rarely happen by chance; it does not say how large or how useful the difference is.
- 90.2 vs 61.3 out of 100 free of a major event at 4 years with AREN0533 Regimen M compared with NWTS-5 (historical); 28.9 more per 100.
- Roughly one extra person helped for every 3 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- These results apply to the people the trial enrolled: Stage III-IV favourable-histology Wilms tumour: response-based omission of lung radiotherapy after complete lung nodule response; augmented chemotherapy (Regimen M) for incomplete response or 1p/16q loss of heterozygosity. People in a different situation may not see the same effect.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
395 participants enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| 4-year event-free survival (all lung-metastasis patients)primary | AREN0533 risk-adapted | 292 | 85.4% | — | <0.001 | link |
| NWTS-5 (historical) | — | 72.5% | ||||
| 4-year event-free survival, LOH 1p/16q stage III-IV, Regimen M | AREN0533 Regimen M | 51 | 90.2% | — | — | link |
| NWTS-5 (historical) | — | 61.3% |
Pages like this
not linked directly; found by shared links- TrialCOG ACNS0331
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