التفاصيل البيبلوغرافية
| العنوان: |
Influence of tumor mutational burden, inflammatory gene expression profile, and PD-L1 expression on response to pembrolizumab in head and neck squamous cell carcinoma |
| المؤلفون: |
Haddad, Robert I, Seiwert, Tanguy Y, Chow, Laura Q M, 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, Mehra, Ranee |
| المساهمون: |
Merck & Co., Inc. |
| المصدر: |
Journal for ImmunoTherapy of Cancer ; volume 10, issue 2, page e003026 ; ISSN 2051-1426 |
| بيانات النشر: |
BMJ |
| سنة النشر: |
2022 |
| الوصف: |
Background 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. Methods Associations between biomarkers (tumor mutational burden (TMB), neoantigen load (NL), 18-gene T-cell-inflamed gene expression profile (Tcell inf GEP), 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). Results TMB, clonality-weighted TMB, and Tcell inf GEP 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 Tcell inf GEP (Spearman ρ=–0.026) or TMB and PD-L1 (Spearman ρ=0.009); a correlation was observed between Tcell inf GEP 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. Conclusions TMB and inflammatory biomarkers (Tcell inf GEP 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. Trial registration number NCT01848834 . |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1136/jitc-2021-003026 |
| الإتاحة: |
https://doi.org/10.1136/jitc-2021-003026Test |
| حقوق: |
http://creativecommons.org/licenses/by-nc/4.0Test/ |
| رقم الانضمام: |
edsbas.7F5AC6F |
| قاعدة البيانات: |
BASE |
