ctDNA-guided adjuvant radiation for patients with HPV-related oropharyngeal cancer: First planned interim analysis of a phase II multisite study.

Abstract

e18080 Background: Patients with early-stage HPV-related oropharyngeal squamous cell carcinoma (HPV-OPSCC) have favorable outcomes when treated with transoral surgery (TOS) and pathology-guided adjuvant radiotherapy (RT). Circulating tumor HPV DNA (ctHPVDNA) is a sensitive biomarker of tumor recurrence. We designed a phase II study (NCT05387915) to determine if ctHPVDNA can select pathologic intermediate-risk patients for whom adjuvant RT dose could be safely reduced. We report the first interim safety analysis. Methods: Patients with detectable pre-operative ctHPVDNA and pT0-2, N0-1, M0 HPV-OPSCC after TOS resection and neck dissection were screened. Patients with intermediate-risk criteria (close margin (<5 mm), perineural invasion, 2 – 4 positive nodes, or a single lymph node > 3 cm) were eligible. Only patients with no or limited smoking history (<10 pack-year or <30 pack-year if >10 years from smoking cessation) were eligible. Patients with any extranodal extension or positive margin were excluded. ctHPVDNA was drawn post-operatively: if undetectable, patients received 36 Gy in daily 2.4 Gy fractions, if detectable, patients received 50 – 60 Gy in daily 2.0 Gy fractions. In patients with a final surgical margin >2 mm, RT could be omitted to the primary site. The primary endpoint is MDADI composite score at 1-year. Interim safety analyses (with a plan to close the study if 6-month locoregional control <85% at either timepoint) were included after 15 and 30 patients reach 6 months of follow-up post RT. Results: A total of 35 patients have been accrued; we report our first interim safety analysis including 15 patients with at least 6 months of follow-up after RT. The median age was 57 years (range 33 – 74 years), all (15; 100%) were male, 8 (53%) had T1 disease, all (15; 100%) had N1 disease, and 10 (67%) had base of tongue primary tumors. Two patients (13%) had detectable post-operative ctHPVDNA and were treated at discretion of treating radiation oncologist. All other patients (n = 13) had an undetectable post-operative ctHPVDNA and received 36 Gy of adjuvant RT. The six-month locoregional control rate is 100%, fulfilling the first interim safety analysis. With a median follow-up of 12.5 mo (range 9.3 – 24.7 mo), there have been no locoregional failures among the first 15 patients. Conclusions: Among patients with early-stage HPV-OPSCC undergoing TOS and neck dissection with intermediate-risk pathologic features, ctHPVDNA-guided de-escalation of adjuvant RT does not appear to result in an unacceptable risk of early locoregional recurrence. The study will remain open. Clinical trial information: NCT05387915 .