Tumor-informed ctDNA assay to predict recurrence in locally advanced SCCHN

BackgroundDespite multimodal treatment, locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN) has a recurrence rate of ∼50%. Circulating tumor DNA (ctDNA) has emerged as a potential biomarker for molecular residual disease (MRD) detection to identify the patients at a high risk of relapse.MethodsA personalized, tumor-informed, 16-plex mPCR-NGS assay (Signatera™, Natera, Inc.) was used for the detection of ctDNA in plasma samples collected at pre-treatment and within 12 weeks from the completion of curative intent treatment (MRD time point) from patients with clinical stage III-IVB SCCHN. The primary endpoint was recurrence-free survival (RFS) of MRD-positive and negative patients. The secondary endpoint was overall survival (OS) of MRD-positive and negative patients.ResultsPersonalized ctDNA assays were successfully designed for 43 of the 50 patients who underwent curative intent treatment. A total of 86 plasma samples from 43 patients were analyzed in this study. Of the 43 patients with a pre-treatment sample available, ctDNA was detected in 42/43 (97.6%). At the MRD time point, ctDNA was detected in 4 of 42 patients with an MRD time point sample available. Of the 4 MRD-positive patients, three had a recurrence; Of the 38 MRD-negative patients, seven recurred. MRD-positive patients had significantly worse RFS (HR=7.5 95% CI: 1.76-32, p= 0.006) and OS (HR=5.74, 95% CI: 1.04-31.8, p= 0.045) compared to MRD-negative patients.ConclusionsThe personalized, tumor-informed assay can detect ctDNA pre-treatment in patients with LA SCCHN. ctDNA-positivity within 12 weeks of completing curative intent treatment was predictive of worse RFS and OS. These results may open the path to initiating treatment upon molecular recurrence in patients with LA SCCHN.FundingNatera Inc.DisclosureG. Laliotis: Financial Interests, Personal, Full or part-time Employment: Natera, Inc.; Financial Interests, Personal, Stocks/Shares: Natera, Inc.; Non-Financial Interests, Advisory Role: Docus, ai. V. Aushev: Financial Interests, Personal, Full or part-time Employment: Natera, Inc.; Financial Interests, Personal, Stocks/Shares: Natera, Inc. C. Van Marcke de Lummen: Financial Interests, Institutional, Advisory Board: Eli Lilly, Novartis, AstraZeneca; Financial Interests, Institutional, Invited Speaker: Merck; Non-Financial Interests, Member of Board of Directors: BSMO. R. Galot: Financial Interests, Institutional, Invited Speaker: BMS; Other, Travel expenses: Merck, MSD. M.C. Liu: Financial Interests, Institutional, Member: Natera. J. Machiels: Financial Interests, Institutional, Advisory Board: Novartis, MSD, Pfizer, Roche, Debio, AstraZeneca, Innate, Nanobiotix, Bayer, Boehringer Ingelheim, BMS, Pfizer, Cue Pharma, Incyte, Janssen, Johnson & Johnson, ALX Oncology, F-star, nektar, F-star, Seagen, Astellas, Genmab, Merus, GSK, CureVac; Financial Interests, Institutional, Advisory Board, Education: Merck-Serono; Financial Interests, Institutional, Other, Travel expense: Gilead, MSD, sanofi; Financial Interests, Institutional, Steering Committee Member: AstraZeneca, MSD; Financial Interests, Institutional, Coordinating PI: MSD, iTeos, eTheRNA; Financial Interests, Institutional, Local PI: Pfizer, Ceylad, MSD, Novartis, KURA, Roche, Lilly, Boehringer Ingelheim, Sanofi-Aventis, Incyte, Bayer, Merck - Serono, Janssen, Johnson & Johnson, Amgen, Abbvie, GSK; Non-Financial Interests, Leadership Role, Chair: EORTC head and neck group. All other authors have declared no conflicts of interest.