Circulating tumor HPV-DNA dynamics and neoadjuvant chemotherapy with or without nivolumab in viral-mediated oropharyngeal cancer.

Abstract

6091 Background: Human papillomavirus-associated (HPV+) oropharyngeal carcinoma (OPC) is linked to favorable survival outcomes, prompting efforts to de-intensify treatment strategies. Circulating tumor HPV-DNA (ctHPV-DNA) is a promising biomarker for assessing treatment response and guiding de-escalation strategies. This study evaluates how patient characteristics influence ctHPV-DNA dynamics during neoadjuvant therapy across two de-escalation clinical trials. Methods: Patients with non-metastatic HPV+ OPC enrolled across two trials of neoadjuvant carboplatin/paclitaxel (NCT04572100) or carboplatin/ nab -paclitaxel/nivolumab (OPTIMA II, NCT03107182), with ctHPV-DNA available at baseline and post-neoadjuvant, were eligible. All participants received three cycles of neoadjuvant therapy followed by response-adapted de-escalated locoregional treatment. ctHPV-DNA values (copies per ml plasma) were measured at baseline and after 2-3 cycles of neoadjuvant therapy, and percentage reductions were calculated. We defined “ctHPV-DNA clearance” as ≥ 95% reduction from baseline and compared data distribution between patients who achieved clearance and those who did not using Kruskal-Wallis, Pearson’s χ2, or Fisher’s exact tests. Overall survival (OS) and progression free survival (PFS) probabilities were compared using log-rank test. Results: The study included 84 patients . The mean age was 60.9 years. 93% of patients with neoadjuvant nivolumab/chemotherapy achieved ctHPV-DNA clearance compared to 82% with chemotherapy alone, p =0.298. Patients with T1-T2 tumors (AJCC 8 th edition) were significantly more likely to achieve ctHPV-DNA clearance compared to those with T3-T4 tumors ( p =0.0254). Age, race/ethnicity, smoking history, tumor site (e.g., tonsil), and risk group were not significantly associated with ctHPV-DNA clearance rates. ctHPV-DNA clearance by cycle 2-3 of neoadjuvant therapy predicted radiographic response per RECIST v1.1 ( p =0.001), and significantly improved OS ( p =0.025) and PFS ( p <0.001). Survival outcomes were similar across OPTIMA II and NCT04572100 as previously reported. Conclusions: Earlier T-stage tumors were associated with rapid ctHPV-DNA clearance by cycle 2 with a trend towards higher clearance rate with neoadjuvant nivolumab/chemotherapy. Rapid clearance predicts radiographic response, OS, and PFS, supporting ctHPV-DNA as a useful biomarker for treatment monitoring with neoadjuvant treatment in HPV+ OPC. Clinical trial information: NCT03107182 . ctHPV-DNA % reduction between baseline and follow up at cycle 2-3. ≥ 95% reductionN (%) < 95% reductionN (%) p Age, (mean ± sd) 60.4 ± 10 61.3 ± 8.5 0.656 Gender (Male) 59 (86.8) 9 (13.2) 1 Race (Caucasian) 54 (86) 9 (14) 0.583 Risk (High) 34 (92) 3 (8) 0.309 T1 stage 12 (75) 4 (25) 0.0254 T2 stage 30 (97) 1 (3) T3 stage 8 (89) 1 (11) T4 stage 3 (60) 2 (40) Tumor shrinkage (median %, range) -64.2 (-23, -100) -42 (-14, -71) 0.001