201. Influence of tumor mutational burden, inflammatory gene expression profile, and PD-L1 expression on response to pembrolizumab in head and neck squamous cell carcinoma
- Author
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Haddad, Robert I, Seiwert, Tanguy Y, Chow, Laura QM, Gupta, Shilpa, Weiss, Jared, Gluck, Iris, Eder, Joseph P, Burtness, Barbara, Tahara, Makoto, Keam, Bhumsuk, Kang, Hyunseok, Muro, Kei, Albright, Andrew, Mogg, Robin, Ayers, Mark, Huang, Lingkang, Lunceford, Jared, Cristescu, Razvan, Cheng, Jonathan, and Mehra, Ranee
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Dental/Oral and Craniofacial Disease ,Sexually Transmitted Infections ,Cancer ,Clinical Research ,Good Health and Well Being ,Antibodies ,Monoclonal ,Humanized ,Antineoplastic Agents ,Immunological ,B7-H1 Antigen ,Female ,Head and Neck Neoplasms ,Humans ,Immunotherapy ,Male ,Squamous Cell Carcinoma of Head and Neck ,Transcriptome ,Tumor Burden ,gene expression profiling ,head and neck neoplasms ,immunotherapy ,programmed cell death 1 receptor ,tumor biomarkers ,Oncology and carcinogenesis - Abstract
To characterize genomic determinants of response to pembrolizumab in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) in the KEYNOTE-012 study. Associations between biomarkers (tumor mutational burden (TMB), neoantigen load (NL), 18-gene T-cell-inflamed gene expression profile (TcellinfGEP), and PD-L1 combined positive score (CPS)) and clinical outcomes with pembrolizumab were assessed in patients with R/M HNSCC (n=192). Tumor human papillomavirus (HPV) status was also evaluated with the use of p16 immunohistochemistry and whole exome sequencing (WES; HPV+, mapping >20 HPV reads) in pretreatment tumor samples (n=106). TMB, clonality-weighted TMB, and TcellinfGEP were significantly associated with objective response (p=0.0276, p=0.0201, and p=0.006, respectively), and a positive trend was observed between NL and PD-L1 CPS and clinical response (p=0.0550 and p=0.0682, respectively). No correlation was observed between TMB and TcellinfGEP (Spearman ρ=-0.026) or TMB and PD-L1 (Spearman ρ=0.009); a correlation was observed between TcellinfGEP and PD-L1 (Spearman ρ=0.511). HPV status by WES and p16 immunohistochemistry showed concordance (84% ҡ=0.573) among patients whose HPV results were available using both methods. TMB and inflammatory biomarkers (TcellinfGEP and PD-L1) may represent distinct and complementary biomarkers predicting response to anti-programmed death 1 therapies in HNSCC; further study of these relationships in randomized clinical trials is needed. NCT01848834.
- Published
- 2022