Abstract 882P
Background
Recent evidence has shown that the tight junction protein Claudin-1 (CLDN1) is overexpressed in different solid tumors. CLDN1 can be targeted through specific agents to revert its effects. The present work aims to explore CLDN1 expression in a cohort of HNSCC patients (pts).
Methods
A single center cohort of 100 loco-regionally advanced HNSCC pts included in the BD2Decide project was analyzed [PMID 33107152]. All pts received treatments with curative intent. Primary tumor specimens were profiled for gene expression by Affymetrix ClariomD chips and processed using the Transcriptome Analysis Console Software (ThermoFisher). Normalized and log2 CLDN1 were retrieved from the data matrix and used to analyze: i) data distribution based on anatomical subsites, HPV status, and molecular subtypes assessed by Kruskal-Wallis test; ii) prognostic value having overall survival (OS) as endpoint estimated with Kaplan-Meier method and compared with the log-rank test. Hazard ratios (HR) were estimated with Cox proportional hazard model.
Results
The clinical characteristics of the pts cohort are reported in the following table. Table: 882P
Characteristics | N (%) | |
Sex | M F | 76 (76) 24 (24) |
Median age | 60 years (range 21-80) | |
Primary HNSCC site | Oral cavity HPV+ OPC HPV- OPC Hypopharynx Larynx | 20 (20) 20 (20) 20 (20) 20 (20) 20 (20) |
Stage | HPV+ I II III HPV- HNSCCs III IVa/b | - 6 (30) 6 (30) 8(40) - 25 (31) 55 (69) |
CLDN1 | High (>4.4) Low (<4.4) | 15 (15) 85 (85) |
Median follow-up | 64.44 months [m] (95% CI: 54.24-66.91) | |
Median DFS | Overall HPV+ HPV- CLDN1-high CLDN1-low | 42.79 m (95% CI: 22.5-72.2) 53.91 m (95% CI: 13.09-53.91) 35.53 m (95% CI: 15.43-72.2) 22.9 m (95% CI: 7.96-35.79) 65.1 m (95% CI: 22.5-72.2) |
Median OS | Overall HPV+ HPV- CLDN1-high CLDN1-low | 94.24 m (95% CI: 59.08-94.24) Not reached 72.2 m (95% CI: 43.88-94.24) 26.2 m (95% CI: 14.31-94.24) Not reached |
CLDN1 expression significantly differed (p=0.0158) among HNSCC primary sites (in decreasing order of expression): hypopharynx, HPV+ oropharynx (OPC), larynx, HPV- OPC, oral cavity. Survival was significantly shorter in pts with high vs low CLDN1 (Table): OS HR=3 (95% CI 1.43-6.28, p=0.0023), DFS HR=2.14 (95% CI 1.11-4.11, p=0.02).
Conclusions
CLDN1 expression is heterogeneous in HNSCC pts, and has a prognostic significance. These results may guide pts selection for future clinical studies with anti CLDN1-antobody, which is currently under development.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Funding
The conduction of the clinical study and gene expression analyses were conducted within the BD2Decide research project, which was funded by the European Union Horizon 2020 Framework Program (Grant/Award Number: 689715). The present study submitted as abstract was funded by Alentis.
Disclosure
L.F.L. Licitra: Financial Interests, Institutional, Research Funding, related to the submitted abstract: Alentis; Financial Interests, Personal and Institutional, Other, advisory board and research funding: AstraZeneca; Financial Interests, Institutional, Research Funding: BMS, Boehringer Ingelheim, Celgene International, Eisai, Exelixis, Debiopharm International SA, Hoffmann-La Roche ltd, IRX Therapeutics, Medpace, Novartis, Pfizer, Roche, Adlay Norte Biopharma Co Ltd; Financial Interests, Personal and Institutional, Advisory Board, advisory board and research funding: Merck-Serono, MSD; Financial Interests, Personal, Advisory Board: Bayer, Neutron Therapeutics, Inc. All other authors have declared no conflicts of interest.
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