Abstract 699P
Background
Patients with recurrent head and neck squamous cell carcinoma (HNSCC) have dismal outcomes despite advances in salvage definitive therapies. Aiming to expand our understanding of recurrent HNSCC, we characterize the molecular and immune landscape of HNSCC patients enrolled in a Phase II trial of adjuvant nivolumab after salvage resection (NCT03355560).
Methods
Tissue-based DNA and RNA sequencing utilizing a commercially available CLIA-certified assay (Caris Life Sciences) were used to analyze tissue samples from HNSCC patients enrolled in the trial. NGS, WES and WTS was performed on 37 tumors. TMB cutoff point of ≥10 was used. PD-L1 expression was tested by IHC (22c3 antibody, ≥1 CPS being positive). Statistical significance was determined using Fisher’s-Exact or X2 test with Benjamini-Hochberg correction. Gene expression was analyzed using the Limma R package. Immune cell abundance was measured using Microenvironment Cell Populations-counter (MCP) method.
Results
In patients with recurrent H&N cancers treated with Nivolumab, distinct immune cell abundance and molecular alterations were not found between patients who developed a relapsed disease (n= 11) and those who did not (n= 26). Molecular alterations in TP53 (86%, 100%, 0%; q < 0.01), P1K3CA (0%, 0%, 57%; q< 0.01) and p16 IHC (8%, 0%, 86%; q < 0.01) were detected in tumors from the larynx, oral cavity, and oropharynx. Myeloid dendritic cell (FC= 1.3; p < 0.05) and endothelial cell (FC = 1.2; p < 0.05) abundance were increased in patients who received RT only vs ChemRT. ABCA10 gene expression decreased in patients treated previously with ChemRT (logFC = -1.4; p < 0.05), compared to RT only. TMB-High tumors exhibited increased SNRPFP1 gene expression (logFC = 1.2; p < 0.01). Well differentiated tumors showed increased gene expression in SEMA3G (logFC = 1.4; p < 0.05) and HS3ST6 (logFC = 1.4; p < 0.05) genes compared to poorly/moderately differentiated tumors.
Conclusions
Recurrent HNSCC cancers manifest heterogeneous molecular and immune profiles on subgroups analysis with no clear marker to predict response to Nivolumab in the adjuvant setting. Larger prospective trials are needed to explore this area further.
Clinical trial identification
NCT03355560.
Editorial acknowledgement
Legal entity responsible for the study
Karmanos Cancer Institute and University of Cincinnati Health.
Funding
Has not received any funding.
Disclosure
J.E. McGrath: Financial Interests, Institutional, Full or part-time Employment: Caris Life Sciences. T. Wise-draper: Financial Interests, Personal, Other, Consultant: Shattuck Labs; Financial Interests, Personal, Advisory Board: Exicure, Rakuten Medical, Merck & Co; Financial Interests, Personal, Invited Speaker: Physician Education Resource; Financial Interests, Personal, Other, Consultant for Molecular Tumor Board: Caris Life Sciences; Financial Interests, Personal, Ownership Interest: High Enroll; Financial Interests, Personal, Research Grant: BMS, Merck & Co, Tesaro/GSK, AstraZeneca, Janssen; Financial Interests, Personal and Institutional, Invited Speaker: BMS, EMD Serono, Replimune, AstraZeneca, Alkermes, Exicure, Shattuck Labs, Boston Medical, Debio Pharm, Eli Lilly, Epizyme, Iovance, Agenus, SQZ Biotech, Triumvera, AdlaiNortye, Yingli, Vyriad, Ideaya. P. Walker: Financial Interests, Institutional, Full or part-time Employment: Caris Life. M. Oberley: Financial Interests, Institutional, Full or part-time Employment: Caris Life. All other authors have declared no conflicts of interest.