Tumor-Informed ctDNA Assay to Predict Outcome in Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck Treated with PD-1 Inhibitor.

Abstract

Although immunotherapy improves the overall survival (OS) of patients with recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN), only 15% to 20% of patients derive a long-term benefit. We hypothesized that ctDNA kinetics during immunotherapy, with or without chemotherapy, could predict treatment efficacy in patients with R/M SCCHN. Using a personalized, tumor-informed ctDNA assay, we evaluated ctDNA kinetics from pre- to on-treatment (6-10 weeks after treatment initiation) time points. The primary endpoint was the concordance between ctDNA kinetics and best overall response (BOR). Secondary endpoints were the association of ctDNA clearance and kinetics with OS and progression-free survival (PFS). Of the 41 patients, ctDNA assays were successfully designed for 29, and ctDNA was detected before treatment in 25 patients. ctDNA kinetics was significantly correlated with BOR (P = 0.00032). Patients with unfavorable ctDNA kinetics had significantly worse PFS compared with those with favorable ctDNA kinetics (HR = 16.98; 95% confidence interval, 3.35-86.1; P = 0.0006). Six patients had ctDNA clearance, all of whom presented a complete or partial response as BOR. PFS and OS were significantly improved in patients with ctDNA clearance compared with those without clearance (PFS: P = 0.0006, OS: P = 0.027). ctDNA kinetics, assessed with a tumor-informed assay, can predict anti-PD-1 therapy efficacy in R/M SCCHN. Early ctDNA clearance during the initial weeks of immunotherapy seems to be a strong predictive marker for a favorable response, as well as improved PFS and OS.