Abstract 1778P
Background
UCB has a variable prevalence worldwide. We queried whether UCB arising in pts with SAS ancestry would feature unique genomic features when compared with patients (pts) of other, predominantly European, descent.
Methods
6,107 Global clinically advanced UCB cases underwent comprehensive genomic profiling (CGP) that included ancestry classification using a proprietary ancestry calculation algorithm. All classes of GA were determined on either primary or metastatic disease biopsies using a 324-gene hybrid-capture based method which also calculates tumor mutational burden (TMB) and determines microsatellite status (MSI).
Results
Overall, 70 (1.3%) of patients with UCB were of SAS ancestry. In comparison with the Global pts, the gender distribution was similar, but pts of SAS were older (p<.0001). The GA/tumor were also similar. In addition to lower TERT GA (57% v 77%; P=.0002), pts of SAS had lower frequency of ‘targetable’ GA, including FGFR3 (8.6% v 18.4%; p=.038) as well as non-significantly lower frequency of PIK3CA (17.1% v 22.6%) and ERBB2 (11.4% v 17.9%), PTEN (1.4% v 4.4%) and TSC1 (7.1% v 9.2%). In contrast, pts of SAS had higher frequency of potential immune-oncology (IO) biomarkers, including higher mean TMB (15.5 v 10.3 mut/Mb; p=.002) and TMB > 10 mut/Mb (43.8% v 36.6%; NS). Table: 1778P
| UCB Global | UCB SAS | P Value | |
| Cases | 1,760 | 70 | |
| Male/Female | 74%/26% | 74%/26% | |
| Mean age | 71 | 77 | <.0001 |
| GA/tumor | 8.17 | 8.78 | NS |
| CDKN2A | 38.1% | 32.8% | NS |
| TP53 | 60.6% | 68.3% | NS |
| RB1 | 20.1% | 20.1% | NS |
| TERT | 77.4% | 57.1% | =.0002 |
| ARID1A | 24.8% | 18.4% | NS |
| FGFR3 | 18.4% | 8.6% | =.038 |
| PIK3CA | 22.6% | 17.1% | NS |
| ERBB2 | 17.9% | 11.4% | NS |
| PTEN | 4.4% | 1.4% | NS |
| TSC1 | 9.2% | 7.1% | NS |
| BRCA1 | 2.1% | 2.8% | NS |
| BRCA2 | 2.6% | 2.8% | NS |
| MTAP | 25.0% | 15.7% | =.09 |
| CD274 | 1.2% | 0% | NS |
| MDM2 | 9.0% | 10.0% | NS |
| MSI High | 0.7% | 0% | NS |
| Mean TMB | 10.3 | 15.4 | =.002 |
| TMB≥10 mut/Mb | 36.6% | 43.8% | NS |
| TMB≥20 mut/Mb | 12.4% | 12.5% | NS |
Conclusions
At less than 2.5 cases per 100,000 population, UCB is an extremely uncommon disease in SAS pts. However, when UCB occurs in the advanced setting, it seems to have unique features when compared to UCB in North America and Western Europe, including significantly reduced opportunities for targeted therapies, but potentially higher chance for response to IO-based therapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Foundation Medicine Inc.
Disclosure
P. Grivas: Financial Interests, Personal, Advisory Board: AstraZeneca, Merck, Bristol Myers Squibb, Clovis Oncology, EMD Serono, Seattle Genetics, Pfizer, Janssen, Genzyme, Mirati Therapeutics, Exelixis, Genentech/Roche, GlaxoSmithKline, Immunomedics, Dyania Health, Infinity Pharmaceuticals, QED Therapeutics, 4D Pharma PLC; Financial Interests, Personal, Other, consulting: Foundation Medicine; Financial Interests, Institutional, Invited Speaker: Pfizer, Clovis Oncology, Bavarian Nordic, Immunomedics, Bristol Myers Squibb, Debiopharm Group, Merck, QED Therapeutics, GlaxoSmithKline, Mirati Therapeutics. A. Necchi: Financial Interests, Institutional, Research Grant: Merck, AstraZeneca, Ipsen, BMS, Gilead; Financial Interests, Personal, Invited Speaker: Roche, Janssen, Bayer, Astellas, AstraZeneca, Merck, Clovis Oncology; Financial Interests, Invited Speaker: Incyte, Pfizer; Non-Financial Interests, Leadership Role: Global society of Rare Genitourinary Tumors (GSRGT). N.A. Danziger: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine Inc.; Financial Interests, Personal, Stocks/Shares: F. Hoffman La-Roche Ltd. D.C. Pavlick, H. Tukachinsky, R. P. Graf: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine Inc.; Financial Interests, Personal, Stocks/Shares: Roche. J.S. Ross: Financial Interests, Personal, Full or part-time Employment, Medical Director: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche Holdings, Tango Therapeutics, Celsius Therapeutics. All other authors have declared no conflicts of interest.