Meeting
2020 Genitourinary Cancers Symposium
Comprehensive genomic profiling (CGP) in post-systemic treatment (Post) metastatic sites (MET) and pretreatment (Pre) primary tumors (PT) of metastatic prostate cancer (mPC).
Authors
Andrea Necchi
Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Andrea Necchi , Petros Grivas , Gennady Bratslavsky , Oleg Shapiro , Joseph Jacob , Ethan Sokol , Jo-Anne Vergilio , Keith Killian , Douglas I. Lin , Shakti H. Ramkissoon , Eric Allan Severson , Amanda Hemmerich , Jon Chung , Brian Michael Alexander , Prasanth Reddy , Kimberly McGregor , Julia Andrea Elvin , Alexa Betzig Schrock , Natalie Danziger , Jeffrey S. Ross
Organizations
Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, University of Washington, School of Medicine, Seattle, WA, Urologic Oncology Branch, National Cancer Institute at the National Institutes of Health, Bethesda, MD, SUNY Upstate Medical University, Syracuse, NY, Foundation Medicine, Inc., Cambridge, MA, Foundation Medicine Inc, Cambridge, MA, Foundation Medicine, Cambridge, MA, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston, MA, Univ of Utah Huntsman Cancer Inst, Corvallis, OR, Foundation Medicine Inc., Cambridge, MA
Research Funding
Pharmaceutical/Biotech Company
Foundation Medicine Inc
Background: CGP was performed on Pre PT and Post MET including bone (BO), liver (LIV), lung (LU), brain (BN), lymph node (LN) and soft tissue (ST) mPC. Methods: 1,294 mPC underwent hybrid-capture based CGP. Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. PD-L1 expression was determined by IHC (Dako 22C3). Results: GA in AR were lowest in the Pre PT (2%) and highest in Post LU (24%) and LIV (50%). GA/tumor was significantly higher in BN (8.0) compared to PT (3.8). BR MET also featured higher PTEN GA than PT. BRCA2 GA varied from 0% in BR to 7-9% in PT, BO, LU, LN and ST to a high of 15% in LI MET. ATM GA were significantly higher in LU MET and RAD21 GA highest in LN MET. Potential predictors of IO drug response included high CDK12 GA in LU MET, MSI high status at 29% in BR MET associated with higher TMB levels, but virtual absence of high PD-L1 expression. ERBB2 GA appeared to be increased in the MET group compared with PT but BRAF GA were not. RB1 GA were significantly increased in LIV MET cases. Conclusions: CGP of mPC PT and MET demonstrates significant differences likely linked to exposure to systemic therapies. These findings suggest that, in the future, liquid biopsies may have advantages over individual MET site biopsies in their ability to capture the entire range of therapeutic opportunities for patients with advanced mPC.
| Pre | Post | LIV | LU | BN | LN | ST | |
|---|---|---|---|---|---|---|---|
| PT | BO | ||||||
| Cases | 770 | 127 | 34 | 25 | 7 | 205 | 126 |
| Median age (range) | 64 (39-89+) | 68 (44-89+) | 69 (48-84) | 70 (50-86) | 75 (58-84) | 68 (39-89+) | 68 (44-89+) |
| GA/tumor | 3.8 | 5.0 | 5.1 | 4.2 | 8.0 | 4.8 | 5.0 |
| TMPRSS2:ERG | 35% | 27% | 32% | 32% | 29% | 40% | 27% |
| AR | 2% | 31% | 50% | 24% | 43% | 33% | 31% |
| TP53 | 37% | 41% | 56% | 28% | 57% | 50% | 41% |
| PTEN | 24% | 38% | 38% | 32% | 86% | 42% | 38% |
| BRCA2 | 9% | 8% | 15% | 8% | 0% | 7% | 8% |
| ATM | 6% | 6% | 0% | 24% | 0% | 5% | 6% |
| RAD21 | 9% | 6% | 9% | 8% | 0% | 11% | 6% |
| MYC | 7% | 10% | 9% | 8% | 14% | 18% | 10% |
| PIK3CA | 7% | 6% | 3% | 8% | 14% | 6% | 6% |
| RB1 | 4% | 9% | 30% | 0% | 0% | 5% | 9% |
| APC | 8% | 12% | 18% | 8% | 29% | 6% | 10% |
| CDK12 | 5% | 10% | 0% | 16% | 0% | 5% | 10% |
| BRAF | 4% | 3% | 6% | 0% | 0% | 3% | 3% |
| ERBB2 | 0.6% | 5% | 3% | 8% | 0% | 2% | 5% |
| MSI-High | 2% | 5% | 7% | 0% | 29% | 2% | 5% |
| Median TMB | 1.3 | 2.5 | 2.5 | 2.5 | 7.5 | 2.5 | 2.5 |
| TMB>10/20 mut/Mb | 5%/3% | 7%/4% | 9%/3% | 0%/0% | 43%/29% | 4%/2% | 7%/4% |
| PD-L1 IHC Low Positive | 8%/0% | 3%/0% | 15%/0% | 13%/0% | 0%/0% | 4%/4% | 3%/0% |
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Abstract Details
Session Type
Poster Session
Session Title
Poster Session A: Prostate Cancer
Track
Prostate Cancer - Advanced,Prostate Cancer - Localized
Sub Track
Tumor Biology, Biomarkers, and Pathology
Citation
J Clin Oncol 38, 2020 (suppl 6; abstr 175)
Abstract #
175
Poster Bd #
H11
Abstract Disclosures
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