{"entity":{"id":"aren0533","kind":"trial","name":"COG AREN0533","aka":[],"tldr":"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.","summary":"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.","status":"positive","asOf":"2026-09-10","links":[{"label":"ClinicalTrials.gov NCT00379340","url":"https://clinicaltrials.gov/study/NCT00379340"},{"label":"Dix et al., JCO 2018 (lung metastases)","url":"https://doi.org/10.1200/JCO.2017.77.1931"},{"label":"Dix et al., JCO 2019 (LOH 1p/16q)","url":"https://doi.org/10.1200/JCO.18.01972"}],"tags":["nci-coverage","paediatric","kidney"],"related":[],"cancers":["wilms-tumor"],"sections":[],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":["vincristine","dactinomycin","doxorubicin","cyclophosphamide","etoposide"],"companies":["childrens-oncology-group"],"institutions":[],"pathways":[],"terms":["de-escalation","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":["paper-dix-j-clin-oncol","paper-dix-j-clin-oncol-2018"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT00379340","phase":"3","setting":"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","sponsor":"Children's Oncology Group","result":"Overall 4-year EFS 85.4% and OS 95.6% (vs 72.5% and 84.0% in NWTS-5); 4-year EFS 90.2% for LOH 1p/16q stage III-IV with augmented therapy.","started":"2007-04-30","startedType":"actual","yearReported":2018,"enrolled":395,"enrolledBasis":"registry","outcomes":[{"endpoint":"4-year event-free survival (all lung-metastasis patients)","primary":true,"unit":"%","arms":[{"name":"AREN0533 risk-adapted","n":292,"value":85.4},{"name":"NWTS-5 (historical)","value":72.5}],"p":"<0.001","source":"https://doi.org/10.1200/JCO.2017.77.1931"},{"endpoint":"4-year event-free survival, LOH 1p/16q stage III-IV, Regimen M","unit":"%","arms":[{"name":"AREN0533 Regimen M","n":51,"value":90.2},{"name":"NWTS-5 (historical)","value":61.3}],"source":"https://doi.org/10.1200/JCO.18.01972"}],"replication":"Non-randomised against historical NWTS-5 controls; the SIOP-RTSG UMBRELLA protocol in Europe pursues the same response- and biology-adapted logic."},"route":"/trials/aren0533/","neighbours":{"cancer":[{"id":"wilms-tumor","kind":"cancer","name":"Wilms tumour (nephroblastoma)","route":"/cancers/wilms-tumor/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"}],"drug":[{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"dactinomycin","kind":"drug","name":"Dactinomycin (actinomycin D)","route":"/drugs/dactinomycin/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"etoposide","kind":"drug","name":"Etoposide","route":"/drugs/etoposide/"},{"id":"vincristine","kind":"drug","name":"Vincristine","route":"/drugs/vincristine/"}],"company":[{"id":"childrens-oncology-group","kind":"company","name":"Children's Oncology Group (COG)","route":"/companies/childrens-oncology-group/"}],"term":[{"id":"de-escalation","kind":"term","name":"De-escalation, escalation and response-adapted therapy","route":"/terms/de-escalation/"},{"id":"late-effects","kind":"term","name":"Late effects and survivorship toxicity","route":"/terms/late-effects/"}],"bottleneck":[{"id":"b-survivorship","kind":"bottleneck","name":"Survivorship and late effects are neglected","route":"/bottlenecks/b-survivorship/"}],"paper":[{"id":"paper-dix-j-clin-oncol","kind":"paper","name":"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","route":"/key-papers/paper-dix-j-clin-oncol/"},{"id":"paper-dix-j-clin-oncol-2018","kind":"paper","name":"Treatment of Stage IV Favorable Histology Wilms Tumor With Lung Metastases: A Report From the Children's Oncology Group AREN0533 Study","route":"/key-papers/paper-dix-j-clin-oncol-2018/"}],"trial":[{"id":"ccss","kind":"trial","name":"Childhood Cancer Survivor Study (CCSS)","route":"/trials/ccss/"}],"roadmap":[{"id":"paediatric-oncology-roadmap","kind":"roadmap","name":"Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first","route":"/roadmaps/paediatric-oncology-roadmap/"}]}}