Circulating tumor DNA (ctDNA) as a biomarker for pathologic response and clinical outcomes in patients with cutaneous squamous cell carcinoma (CSCC) receiving neoadjuvant anti–PD-1 therapy.

9587 Background: ctDNA is a novel biomarker that can be used to evaluate recurrence and treatment response in multiple cancers. The utility of ctDNA in patients with CSCC receiving neoadjuvant immunotherapy (nIT) is unknown. Methods: In this retrospective study, we examined patients with CSCC who received nIT and had ctDNA assay available pre- and post- operatively. Positive ctDNA was defined as a value >0, and ctDNA sensitivity pre-operatively (pre-op) was reported in all patients. Patients with at least two ctDNA measurements pre-op were classified into two cohorts: cohort-A included patients whose ctDNA decreased; Cohort-B included patients whose ctDNA increased. Pathologic response (PR) was defined as complete (pCR) if 0% viable tumor vt, major (mPR) if vt 10%. The association between ctDNA kinetics during the pre-op period nIT and PR was analyzed using Fisher’s exact test. During the post-op period, we used minimal residual disease (MRD) status defined by positive ctDNA measurement within 3 months post-op. Recurrence-free survival (RFS) (landmark analysis with time starting at post-MRD timepoint until recurrence, death or loss-to follow-up) was compared between patients who had detectable MRD (positive ctDNA within 3 months post-op) versus those who had undetectable MRD. Results: Forty nine patients were included of which 42 (85.7%) were male, 11 (22.4%) were immunosuppressed, and 31 (63.3%) had AJCC stage IV CSCC. The median follow-up time since starting nIT was 12.9 months. The ctDNA sensitivity at baseline (prior to starting nIT) was 79.6%. The median number of ctDNA collections per patient was 6 (range: 1, 21). Of the 49 patients who underwent surgery, 38 were eligible who had at least 2 ctDNA measurements pre-op. Cohort-A (35 patients) had higher cPR and mPR compared to cohort-B (3 patients) (p=0.05). When excluding 3 patients who did not have kinetic ctDNA changes (ctDNA value was 0 at all pre-op time points), ctDNA decrease was significantly associated with cPR and mPR (p= 0.03). For post-op period, patients with detectable MRD (n=5) had significantly lower RFS compared to those with undetectable MRD (median RFS 11.3 months vs. not reached, HR: 11.9; 95% CI: 2.2-65.8; p< 0.01)(Table). Conclusions: ctDNA changes and detectable MRD may be suitable biomarkers for pathologic response assessment and post-op period in patients with CSCC receiving nIT. Further research is essential to confirm these findings. Recurrence-free survival according to MRD status. MRD status N Median after 3-month post-op (95% CI) month 6-month RFS after 3-month post-op (95% CI) months 12-month RFS after 3-month post-op (95% CI) months Hazard ratio (95% CI) Negative 31 NA (NA, NA) 0.96 (0.89, 1) 0.89 (0.74, 1) ref Positive 5 11.3 (2.22, NA) 0.6 (0.29, 1) 0.3 (0.06, 1) 11.9 (2.2, 65.8)