Abstract

Immune checkpoint inhibition (ICI) is a clinically effective FDA-approved therapy for advanced basal cell carcinoma (BCC). Tumor and clinical characteristics that predict ICI efficacy remain undefined. Tumor mutational burden (TMB), PD-L1 status, and molecular signatures have been associated with better ICI efficacy. This study sought to characterize the genetic changes of advanced BCC and identify clinical characteristics of tumors with higher TMB. Formalin fixed paraffin embedded tissue from 243 clinically advanced BCCs underwent hybrid-capture based comprehensive genomic profiling to evaluate for genomic alterations. Patient demographics and tumor anatomic location were documented. Specimens included primary tumors (n=172), lymph node metastases (n=16), and distant metastases (n=55). Median TMB was found to be 40.0 mutations/Mb and similar between primary and metastatic sites. BCCs from the extremities had higher TMB when compared with non-extremity cases (median 59.0 v. 31.1 mut/Mb, p=.047). BCCs from males had higher TMB than BCCs from females (median 44.7 v. 22.6 mut/Mb, p=.028). Metastatic BCC sites were observed more commonly in men than women (34.0% v 19.8%, p=.0248). When analyzing primary tumors only, BCCs from males again demonstrated higher TMB (median 44.4 v 18.8, p=.0079). PD-L1 staining was performed in 52 cases and noted higher frequency in BCCs from male patients (12.5% [4/32] vs. 5% [1/20], p=.28). We conclude that advanced BCC from extremity primary sites and from men demonstrate elevated TMB. These results may direct future studies to evaluate if site or sex influence response to anti-PD-1 immunotherapy.

Financial Disclosure: No current or relevant financial relationships exist.