1. Phenotypic and Genomic Determinants of Immunotherapy Response Associated with Squamousness.
- Author
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Goodman AM, Kato S, Chattopadhyay R, Okamura R, Saunders IM, Montesion M, Frampton GM, Miller VA, Daniels GA, and Kurzrock R
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Immunological pharmacology, Antineoplastic Agents, Immunological therapeutic use, Biomarkers, Tumor, California epidemiology, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung epidemiology, Female, Genomics methods, Humans, Lung Neoplasms drug therapy, Lung Neoplasms epidemiology, Male, Middle Aged, Molecular Targeted Therapy, Mutation, Prognosis, Treatment Outcome, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Genetic Variation, Lung Neoplasms genetics, Lung Neoplasms pathology, Phenotype
- Abstract
Advanced and metastatic squamous cell carcinomas (SCC) are common and difficult-to-treat malignancies. We assessed 75 immunotherapy-treated patients with SCC from a clinically annotated database of 2,651 patients, as well as 9,407 patients from a deidentified database for molecular features that might influence checkpoint blockade response. SCCs had higher tumor mutational burdens (TMB) than non-SCCs ( P < 0.0001). Cutaneous SCCs had the highest TMB ( P < 0.0001), with 41.3% demonstrating a very high TMB (≥50 mutations/Mb). In immunotherapy-treated patients with SCC, higher TMB (≥12 mutations/Mb) correlated with a trend to higher clinical benefit rate [stable disease ≥ 6 months or partial/complete remission; 60% vs. 29%; (high vs. low TMB); P = 0.06] and significantly longer median time-to-treatment failure (TTF; 9.9 vs. 4.4 months; P = 0.0058). Cutaneous SCCs had the highest clinical benefit [11/15 patients (73%) vs. 20/60 (33%) non-cutaneous ( P = 0.008)], TTF ( P = 0.0015), and overall survival ( P = 0.06) with immunotherapy treatment. In conclusion, among a diverse set of SCCs, higher TMB and cutaneous disease associated with better immunotherapy outcome., (©2019 American Association for Cancer Research.)
- Published
- 2019
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