Faculty Collaboration Database

Phenotypic and Genomic Determinants of Immunotherapy Response Associated with Squamousness. Cancer Immunol Res 2019 Jun;7(6):866-873

Date

04/21/2019

Pubmed ID

31003990

Pubmed Central ID

PMC6548620

DOI

10.1158/2326-6066.CIR-18-0716

Scopus ID

2-s2.0-85067219850 (requires institutional sign-in at Scopus site)   21 Citations

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.

Author List

Goodman AM, Kato S, Chattopadhyay R, Okamura R, Saunders IM, Montesion M, Frampton GM, Miller VA, Daniels GA, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Immunological
Biomarkers, Tumor
California
Carcinoma, Non-Small-Cell Lung
Female
Genetic Variation
Genomics
Humans
Lung Neoplasms
Male
Middle Aged
Molecular Targeted Therapy
Mutation
Phenotype
Prognosis
Treatment Outcome