Phenotypic and Genomic Determinants of Immunotherapy Response Associated with Squamousness

• Published in: Cancer immunology research 2019-06, Vol.7 (6), p.866-873
• Main Authors: Goodman, Aaron M, Kato, Shumei, Chattopadhyay, Ranajoy, Okamura, Ryosuke, Saunders, Ila M, Montesion, Meagan, Frampton, Garrett M, Miller, Vincent A, Daniels, Gregory A, Kurzrock, Razelle
• Format: Article
• Language: English
• ISSN: 2326-6066; 2326-6074
• DOI: 10.1158/2326-6066.CIR-18-0716

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 ( < 0.0001). Cutaneous SCCs had the highest TMB ( < 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); = 0.06] and significantly longer median time-to-treatment failure (TTF; 9.9 vs. 4.4 months; = 0.0058). Cutaneous SCCs had the highest clinical benefit [11/15 patients (73%) vs. 20/60 (33%) non-cutaneous ( = 0.008)], TTF ( = 0.0015), and overall survival ( = 0.06) with immunotherapy treatment. In conclusion, among a diverse set of SCCs, higher TMB and cutaneous disease associated with better immunotherapy outcome.