Abstract 688P
Background
Gene expression profiling studies have identified angiogenic and immune sig. with potential predictive value in patients (pts) with advanced ccRCC. We aimed to update the findings of a large multi-institutional genomics database (Barata, ASCO-GU 21), with a focus on tumors with sarcomatoid and rhabdoid features.
Methods
Whole transcriptome sequencing was performed for ccRCC pt samples submitted to a commercial CLIA-certified lab (Caris Life Sciences, Phoenix, AZ) from Feb19-Mar-21. Genomic signatures were identified by tumor GEP and hierarchical clustering based on the validated 66-gene sig. (D’Costa et al, 2020). Histology reflects both local and central pathology review.
Results
Final analysis included 506 pts [median age 62 (range 19-90), 69.8% men] with ccRCC based on tissue samples from kidney (50%), lung (11.4%), bone (8.5%), liver (4.3%) or other sites (25.6%). GEP identified angiogenic, mixed and T-effector subgroups in 23.5%, 53.2% and 23.3%, respectively. Tumors expressing an angiogenic sig. were more commonly found in pancreatic/small bowel metastases (p=0.01), older pts (p=0.004) and associated with PBRM1 mutations and endothelial cell population abundance. T-effector sig. tumors were found more frequently in men (p=0.0012), kidney (p=0.001), associated with all immunotherapy markers [dMMR/MSI (p=0.0293), TMB (P=0.0292), PD-L1 (P<0.0001)], immunogenic cell population and immune checkpoint abundance as well as BAP1 (p<0.0014), NF2 (p=0.0295) and TP53 (p=0.0162) alterations. A subset of tumors had sarcomatoid and/or rhabdoid features (8.5%) and demonstrated a higher prevalence of the T-effector (48.8%) compared with angiogenic (7.0%) sig. and associated with immunogenic cell population and immune checkpoint gene expression abundance: T cells (p=0.03), cytotoxic lymphocytes (p=0.04), CTLA4 (p=0.02), LAG3 (p=0.004) and PDCD1 (p=0.03).
Conclusions
Our updated real-world dataset confirms the presence of distinct RCC genomic sig. associated with potential markers of immune and angiogenic sensitivity. Prospective validation of these GEPs in therapeutic RCC clinical trials are warranted.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
P.M. Coelho Barata.
Funding
Has not received any funding.
Disclosure
P.M. Coelho Barata: Financial Interests, Institutional, Advisory Board: EMD Serono; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: BlueEarth Pharmaceuticals; Financial Interests, Institutional, Speaker’s Bureau: Bayer; Financial Interests, Institutional, Speaker’s Bureau: Caris Life Sciences; Financial Interests, Institutional, Advisory Board: Dendreon; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Advisory Board: Astellas; Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb; Financial Interests, Institutional, Advisory Board: Pfizer. A. Elliott: Financial Interests, Personal, Member: Caris Life Sciences. R. McKay: Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Tempus; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Calithera; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Tempus; Financial Interests, Personal, Expert Testimony: Dendreon; Financial Interests, Personal, Expert Testimony: Vividion. H.J. Hammers: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: ARMO bioSciences; Financial Interests, Personal, Advisory Board: Corvus Pharmaceuticals; Financial Interests, Personal, Advisory Board: Surface Oncology; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb. M.A. Bilen: Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Calithera Biosciences; Financial Interests, Personal, Advisory Board: Genomic Health; Financial Interests, Personal, Advisory Board: Nektar; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Institutional, Research Grant: Xencor; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Genentech/Roche; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: Tricon Pharmaceuticals; Financial Interests, Institutional, Research Grant: Genome & Company; Financial Interests, Institutional, Research Grant: AAA; Financial Interests, Institutional, Research Grant: Peloton Therapeutics; Financial Interests, Institutional, Research Grant: Pfizer. K. Poorman: Financial Interests, Personal, Affiliate: Caris Life Sciences. T. Zhang: Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Janseen; Financial Interests, Institutional, Research Grant: Acerta; Financial Interests, Institutional, Research Grant: Abbvie; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Merrimack; Financial Interests, Institutional, Research Grant: OmniSeq; Financial Interests, Institutional, Research Grant: PGDx; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Mirati; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Regeneron; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Personal, Advisory Board: Genomic Health; Financial Interests, Personal, Advisory Board: Sanofi Aventis; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Foundation Medicine; Financial Interests, Personal, Advisory Board: Janseen; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: MJH Associates; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Pharmacyclics; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Calithera; Financial Interests, Personal, Advisory Board: Dendreon. W.M. Korn: Financial Interests, Personal, Member: Caris Life Sciences. C. Nabhan: Financial Interests, Personal, Member: Caris Life Sciences. All other authors have declared no conflicts of interest.