Abstract

BackgroundTumour molecular profiling in HNSCC is not routinely incorporated into clinical practice due to lack of validated biomarkers. Liquid biopsy represents noninvasive approach to capture tumour heterogeneity and evolution during treatment. We utilized highly sensitive sequencing method, SafeSEQ, to evaluate plasma circulating tumour DNA (ctDNA) in 2 cohorts of HNSCC patients (pts) with locally advanced (LA) and metastatic disease. MethodsCohort 1 included 54 pts with LA HNSCC treated with cisplatin chemoradiotherapy. Plasma was obtained at baseline, end of treatment (EOT) and disease progression (PD) and compared to baseline tissue mutation status. Cohort 2 included 15 pts with metastatic disease who received nivolumab, plasma results were compared at baseline and post 2ndcycle. Sequencing for p53, CDKN2A, HRAS and PIK3CA was performed with SafeSEQ on both plasma and tissue specimens. Results51/54 pts with LA disease were evaluated at baseline for tissue (t) and plasma (p) mutation status. P53 was the most common mutation (t: 49%), p: 39%) followed by CDKN2A (t: 17.6%,p: 4%), PIK3CA (t: 9.8%, p: 6%) and HRAS (t: 7.8%, p: 4%). Interestingly 3 (5.8%) pts had detectable HRAS mutations in plasma that were not detected in tissue at baseline. In LA pts whose tumor harbored mutation, ctDNA was detectable in 56% at baseline. Concordance of mutation results between baseline plasma and tissue was 51%. At PD (N=10) ctDNA exhibited higher rate of detectability compared to baseline and novel mutations emerged in 40% of cases. In cohort 2, 93% (14/15) of metastatic pts exhibited a detectable plasma mutation prior to and during treatment with nivolumab (p53 (100%), CDKN2A (28.6%), HRAS (21%) and PI3KCA (7%)). The pt with no mutation detected was HPV+. During treatment, new plasma HRAS mutations emerged in 3 (21%) pts, while nivolumab did not modulate the overall mutation profile. There was trend for better PFS in pts of cohort 1 whose tumors contained none of analyzed mutations (p=0.08) while disruptive p53 mutation status based on Poeta classification was not prognostic. ConclusionsPlasma mutation detection with SafeSEQ is useful in HNSCC for molecular profiling and real-time disease monitoring and may inform clinical trial design. Legal entity responsible for the studyUniversity funding & Company. FundingSysmex-inostics. DisclosureD. Edelstein: Full / Part-time employment: Sysmex-Inostics. K. Stieler: Full / Part-time employment: Sysmex-Inostics. D. Heim: Full / Part-time employment: Sysmex-inostics. F. Holtrup: Full / Part-time employment: Sysmex-inostics. A. Psyrri: Research grant / Funding (institution): Kura; Research grant / Funding (institution): BMS; Advisory / Consultancy: BMS; Honoraria (self): BMS; Honoraria (self): MSD; Advisory / Consultancy: MSD; Honoraria (self): Roche; Advisory / Consultancy: AstraZeneca; Honoraria (self): Leo. All other authors have declared no conflicts of interest.

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