{"entity":{"id":"nrg-hn002-hn005","kind":"trial","name":"NRG-HN002 & NRG-HN005 (HPV+ de-escalation)","aka":[],"tldr":"Attempts to give HPV-positive throat cancer patients less radiation fell short: the standard dose remained better, so de-escalation is not yet routine.","summary":"HN002 (phase 2, 2021) found 60 Gy with weekly cisplatin met its acceptability threshold, but 60 Gy alone did not. HN005 (phase 2/3, presented 2025) was stopped after the de-intensified arms showed diminished progression-free survival while the 70 Gy control reached 2-year PFS of 98%. HPV status alone is an insufficient selector; ctHPV-DNA and imaging-response-adapted designs are the next approach.","status":"mixed","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03952585","url":"https://clinicaltrials.gov/study/NCT03952585"},{"label":"NRG Oncology HN005 summary","url":"https://www.nrgoncology.org/Home/News/Post/treatment-de-intensification-for-early-stage-hpv-positive-oropharyngeal-cancer-nrg-hn005/"}],"tags":["lesson:de-escalation-needs-better-selection"],"related":[],"cancers":["head-and-neck","oropharyngeal-cancer","hpv-positive-oropharyngeal-cancer"],"sections":[],"technologies":["imrt-igrt"],"targets":[],"drugs":[],"companies":["nrg-oncology"],"institutions":[],"pathways":[],"terms":["hpv-p16"],"trials":[],"people":["quynh-thu-le"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03952585","phase":"2/3","setting":"Low-risk HPV-positive oropharyngeal cancer: reduced-dose radiation (60 Gy) with or without cisplatin, or with nivolumab, vs standard 70 Gy chemoradiation","sponsor":"NRG Oncology / NCI","result":"HN005: de-escalated arms had worse PFS; control 2-year PFS 98%.","started":"2019-10-09","startedType":"actual","yearReported":2025,"enrolledBasis":"registry","outcomes":[{"endpoint":"HN005: progression-free survival at 2 years (phase II non-inferiority)","primary":true,"unit":"%","arms":[{"name":"70 Gy + cisplatin (standard)","n":136,"value":98.1,"note":"Both de-escalated arms failed non-inferiority (HR vs standard 7.42 and 5.55; non-inferiority margin HR 2.4); the trial did not proceed to phase III"},{"name":"60 Gy + cisplatin","n":116,"value":88.6},{"name":"60 Gy + nivolumab","n":132,"value":90.3}],"source":"https://clinicaltrials.gov/study/NCT03952585"},{"endpoint":"HN002: progression-free survival at 2 years (randomised phase II vs 85% historical control)","unit":"%","arms":[{"name":"60 Gy IMRT + weekly cisplatin","value":90.5,"note":"306 patients; only the cisplatin arm met the PFS and swallowing (MDADI) criteria to advance"},{"name":"60 Gy IMRT alone","value":87.6}],"p":"0.04 (IMRT + cisplatin vs 85%)","source":"https://ascopubs.org/doi/10.1200/JCO.20.03128"}],"replication":"HN005 confirmed the HN002 lesson in a randomised comparison: unselected dose de-escalation in HPV-positive oropharynx cancer costs disease control, consistent with the negative De-ESCALaTE and RTOG 1016 cetuximab-substitution trials."},"route":"/trials/nrg-hn002-hn005/","neighbours":{"cancer":[{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"hpv-positive-oropharyngeal-cancer","kind":"cancer","name":"HPV-positive oropharyngeal cancer","route":"/cancers/hpv-positive-oropharyngeal-cancer/"},{"id":"oropharyngeal-cancer","kind":"cancer","name":"Oropharyngeal cancer (tonsil and base of tongue)","route":"/cancers/oropharyngeal-cancer/"}],"technology":[{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"}],"company":[{"id":"nrg-oncology","kind":"company","name":"NRG Oncology","route":"/companies/nrg-oncology/"}],"term":[{"id":"hpv-p16","kind":"term","name":"HPV-positive (p16) head and neck cancer","route":"/terms/hpv-p16/"},{"id":"seamless-adaptive","kind":"term","name":"Seamless, adaptive and Bayesian trial designs","route":"/terms/seamless-adaptive/"}],"person":[{"id":"quynh-thu-le","kind":"person","name":"Quynh-Thu Le","route":"/people/quynh-thu-le/"}],"pairing":[{"id":"hpv-deescalation-caution","kind":"pairing","name":"Caution: de-escalating radiation on HPV status alone","route":"/pairings/hpv-deescalation-caution/"}],"idea":[{"id":"idea-cthpv-adapted-deescalation","kind":"idea","name":"ctHPV-DNA-adapted de-escalation of chemoradiation","route":"/ideas/idea-cthpv-adapted-deescalation/"}],"roadmap":[{"id":"radiation-roadmap","kind":"roadmap","name":"Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH","route":"/roadmaps/radiation-roadmap/"}]}}