Exploratory phase 2 trial of risk-adapted therapy guided by HPV ctDNA in HPV-positive oropharyngeal carcinoma

It is not known whether on-treatment circulating tumor DNA (ctDNA) can be used to personalize radiation dose. The phase 2 ReACT 1.0 trial at Dana-Fraber Cancer Institute (Boston, MA) enrolled 102 patients with HPV-positive oropharyngeal carcinoma (OPC). Intermediate-risk patients (T4 disease of ≥ 10 pack-year smokers with pretreatment HPV ctDNA scores > 200) were reclassified as low-risk if HPV ctDNA cleared by > 95% mid-treatment. All clinically low-risk and reclassified patients received de-intensified (chemo)radiation. The primary outcome was progression-free survival (PFS) among de-escalated patients. Eighty-nine patients received de-escalated treatment (60 low-risk, 29 reclassified). Two-year PFS rate among de-escalated patients with 93% (95% CI 87-99). Post hoc analyses suggested that intermediate-risk patients reclassified as low-risk and treated with de-escalation had distinct HPV ctDNA dynamics and favorable outcomes. The authors conclude that HPV ctDNA is an emerging biomarker that might improve risk stratification for patients with intermediate-risk HPV-positive OPC.