886P - Prospective evaluation of dynamic changes of cell-free HPV-DNA (cfHPV-DNA) in locoregional HPV associated (HPV+) oropharyngeal cancer (OPC) treated with neoadjuvant chemotherapy and response-stratified treatment

Background

Response-adaptive de-escalation is promising to optimize survival while reducing toxicity. cfHPV-DNA in plasma represents a promising biomarker to grade treatment response and monitor for recurrence. We studied the feasibility of dynamic cfHPV-DNA assessment during response-stratified treatment in HPV+ OPC.

Methods

Patients (pts) with locoregional HPV+ OPC were assigned risk category: High risk (HR) [T4, N3, or ≥20 pack-year smoking history (PYH)]; Low risk (LR) [all other pts]. All pts received three cycles of neoadjuvant carboplatin/paclitaxel. Arm A: Single-modality [transoral robotic surgery or radiation alone to 50Gy] for LR with ≥50% response. Arm B: Intermediate de-escalation (chemoradiation (CRT) to 50Gy/cisplatin) for HR with ≥50% response or LR with <50% response. Arm C: Regular dose (CRT to 70Gy/cisplatin) for all others. cfHPV-DNA was assessed during neoadjuvant, CRT, and post-treatment.

Results

Forty-six eligible patients started induction between 2020 and 2022. Median age 62 (range 38-74), 13% female, 22% ≥20PYH smoking, 70% tonsil, 30% base of tongue, 52% HR, and 48% LR. Response rate to induction≥30% shrinkage was 91%, and≥50% shrinkage was 73%. Arm A (n=16), Arm B (n=21), Arm C (n=8). One patient died during induction. At a median follow-up of 15 months, progression free survival (PFS) at 1-year was 93%. By response-stratified treatment, 1-year PFS was 100% among de-escalated (Arm A and B) and 75% among Arm C (p=0.05). cfHPV-DNA was detectable (+) at baseline in 98% of pts. Clearance rate of cfHPV-DNA after 2 cycles was 72% and associated with a 1-year PFS of 100% vs 79% 1-year PFS with (+)cfHPV-DNA (p=0.1). Of 41 patients with at least 1 cfHPV-DNA assessment≥3 months after treatment, n=5 had (+)cfHPV-DNA. All four recurrences were detected by (+)cfHPV-DNA (sensitivity=100%), and positive predictive value was 80% (4/5). Following surgical salvage (n=2), (+)cfHPV-DNA predicted post-operative recurrence.

Conclusions

These findings demonstrate that plasma cfHPV-DNA clearance after two cycles of chemotherapy has prognostic utility. Post-treatment (+)cfHPV-DNA predicts recurrence. Longer follow-up is planned.

Clinical trial identification

NCT04572100.

Editorial acknowledgement

Legal entity responsible for the study

University of Chicago.

Funding

American Cancer Society Institutional Research Grant, Grant Achatz, Nicholas Kokonas.

Disclosure

A.J. Rosenberg: Financial Interests, Personal, Advisory Board: EMD Serono, Novartis, Vaccitech, Eisai, Astellas, Privo, Nanobiotix; Financial Interests, Personal, Invited Speaker: Coherus; Financial Interests, Institutional, Research Grant: Hookipa, BeiGene. F.S. Jones, A. Starus: Financial Interests, Personal, Full or part-time Employment: Sysmex. All other authors have declared no conflicts of interest.