ReACT 1.0 HPV ctDNA (TTMV-HPV DNA) response-adaptive de-escalation delivers 93% 2-year PFS in HPV+ OPC

LBx-guided risk-adapted therapy: ReACT 1.0 (exploratory Phase II; NCT04900623) enrolled 102 patients with HPV-positive oropharyngeal carcinoma and used on-treatment HPV circulating tumor DNA (ctDNA) kinetics to “rescue” select intermediate-risk patients (T4 and/or >10 pack-years with high baseline HPV ctDNA score >200) into a de-intensification pathway if mid-treatment ctDNA dropped >95%. Overall, 89 patients received de-escalated (chemo)radiation (60 clinically low-risk; 29 reclassified intermediate→low-risk), with 2-year PFS of 93% (95%CI, 87-99) plus favorable post-hoc outcomes in the reclassified cohort; safety/tolerability endpoints were assessed but key Grade 3+ AE/discontinuation rates are not provided in the abstract. As a sanity-check benchmark, de-intensified definitive CRT in NRG-HN002 (60 Gy + weekly cisplatin, low-risk HPV+ OPSCC with ≤10 pack-years) delivered 2-year PFS 86% (with a historical control target of 85%), while post-op de-escalation in ECOG-ACRIN E3311 reported ~95% 2-year PFS in intermediate-risk patients treated with 50-60 Gy—so ReACT’s 93% 2-year PFS looks broadly within the “successful de-escalation” range, but it’s a single-arm, ctDNA-selected strategy that needs randomized confirmation.