Abstract 2362
Background
Tumour 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.
Methods
Cohort 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.
Results
51/54 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.
Conclusions
Plasma mutation detection with SafeSEQ is useful in HNSCC for molecular profiling and real-time disease monitoring and may inform clinical trial design.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
University funding & Company.
Funding
Sysmex-inostics.
Disclosure
D. 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.
Resources from the same session
3839 - Fenofibrate impairs pro-tumorigenic potential of cancer stem cell-like cells within drug-resistant prostate cancer cell populations.
Presenter: Tomasz Wróbel
Session: Poster Display session 3
Resources:
Abstract
3842 - Effect of docetaxel-resistance on the reactivity of prostate cancer cells to metformin
Presenter: Jessica Catapano
Session: Poster Display session 3
Resources:
Abstract
5198 - Cell plasticity and taxanes resistance in metastatic prostate cancer: ESRP1 as a predictive biomarker of taxane response
Presenter: Natalia Jimenez
Session: Poster Display session 3
Resources:
Abstract
2981 - Effect of Selumetinib plus AZD8186 treatment on Cabazitaxel sensitivity in docetaxel-acquired resistant metastatic prostate cancer cell lines
Presenter: Vicenc Ruiz de Porras
Session: Poster Display session 3
Resources:
Abstract
2779 - Anti-tumor activity of cediranib, a pan-inhibitor of vascular endothelial growth factor receptors, in pancreatic ductal adenocarcinoma cells
Presenter: Majid Momeny
Session: Poster Display session 3
Resources:
Abstract
1782 - The molecular mechanisms of EpCAM in regulating tumor progression and development of anti-EpCAM antibodies for colon cancer diagnosis and therapy
Presenter: Han-chung Wu
Session: Poster Display session 3
Resources:
Abstract
1322 - Detection of microRNAs as biomarker for anti-EGFR antibody resistance in colon cancer patients
Presenter: Jens Hahne
Session: Poster Display session 3
Resources:
Abstract
1579 - Serum exosomal microRNA-199b-5p as a novel circulating biomarker to predict response of preoperative chemoradiotherapy for locally advanced rectal cancer
Presenter: Dong Won Baek
Session: Poster Display session 3
Resources:
Abstract
1761 - Live biobank of patient-derived organoids from Thai colorectal cancer patients enables clinical outcome prediction
Presenter: Pariyada Tanjak
Session: Poster Display session 3
Resources:
Abstract
3542 - The biological implications of PDCD6 dysregulation in colorectal cancer
Presenter: Romina Briffa
Session: Poster Display session 3
Resources:
Abstract