Abstract 857P
Background
Merkel cell carcinoma is an aggressive neuroendocrine tumor of the skin. Phenotypes include a low mutation and high mutation variant. Standard of care treatments for MCC include cytotoxic chemotherapy and immune checkpoint inhibitors. Presently, there are no targeted therapy options for MCC, however the AACR Project Genie is a large multi-institutional international database of genomic samples of tumors uniquely suited to evaluate rare tumors.
Methods
Individual patient data from AACR Genie versions 11.1 were accessed from the cBioPortal. Variables of interest include demographic data, alterations annotated by OncoKB therapeutic evidence level, and TCGA PanCancer pathway alterations. TMB was estimated was classified by mutations/Megabase as low (<2), intermediate (2-16), or high (>16).
Results
313 MCC patients were identified from the database. Patients were 34.2% (n=107) female. Patients identified race as 91.7% (n=287) white, 2.2% (n=7) African American, and 0.6% (n=2) Asian. Sampled tissue originated from primary tumor in 55% (n=172) verses metastases in 41.9% (n=131). TMB-Low was present in 49.8% (n=156), TMB-Intermediate in 27.5% (n=86), and TMB-high in 24.7 (N=71). The median number of oncogenic alterations were 0 in TMB-Low, 1 in TMB-Intermediate, and 9 in TMB-High. Level 1-3 alterations (alterations supported by trial or evidence in other tumors) were present in 5.1% (n=9) of solid tumors while only 15.1% (n=13) of hematologic malignancies. Level 3A/B alterations (FDA approved drug for use in a biomarker approved indication or approved drug in another indication) were present in 48% (n=34) of TMB-high, 15% (n=13) of TMB-intermediate, and 5% (n=8) of TMB-low. HRAS (n=3; 2%) alterations more frequent in TMB-Low. Alterations frequent in TMB-High were PIK3CA (N=10; 20%), BRCA1/2 (n=7; 14%), PDGFRA (n=3; 6%), ATM (n=4; 8%), and TSC1/2 (n=2; 4%), CHEK1/2 (n=2; 4%), and PTCH1 (n=2; 4%).
Conclusions
While most targetable mutations in MCC were likely passenger alterations in relation to tumor mutational status, there is a subset of MCC which have actionable alterations. These alterations support enrollment or treatment of MCC with targeted therapies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.