Phenotypic and Genomic Determinants of Immunotherapy Response Associated with Squamousness.

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.

journal_name

Cancer Immunol Res

authors

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

doi

10.1158/2326-6066.CIR-18-0716

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

866-873

issue

6

eissn

2326-6066

issn

2326-6074

pii

2326-6066.CIR-18-0716

journal_volume

7

pub_type

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