Meeting
2020 ASCO Virtual Scientific Program
Contrasting genomic profiles in post-systemic treatment metastatic sites (MET), pretreatment primary tumors (PT), and liquid biopsies (LB) of clinically advanced prostate cancer (PC).
Authors
Andrea Necchi
Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Andrea Necchi , Petros Grivas , Gennady Bratslavsky , Oleg Shapiro , Joseph M Jacob , Ethan Sokol , Jonathan Keith Killian , Douglas I. Lin , Shakti H. Ramkissoon , Eric Allan Severson , Richard Huang , Brian Michael Alexander , Jeffrey Venstrom , Venkataprasanth P. Reddy , Kimberly McGregor , Julia Andrea Elvin , Alexa Betzig Schrock , Dean Pavlick , Natalie Danziger , Jeffrey S. Ross
Organizations
Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, University of Washington, 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, Cambridge, MA, Foundation Medicine, Inc, Morrisville, NC
Research Funding
Pharmaceutical/Biotech Company
Foundation Medicine Inc.
Background: Comprehensive genomic profiling (CGP) was done on pre-systemic treatment (pre) PT, post-treatment (post) MET sites and LB in PC to uncover differences in genomic alterations (GA) and potential impact on therapy selection. Methods: 1,294 PC tissues and 782 LB underwent hybrid-capture based CGP. PT biopsies and resections were compared with post-treatment MET biopsies from bone (BO), liver (LIV), lung (LU), brain (BN), lymph node (LN) and soft tissue (ST) sites and LB. TMB was determined on up to 1.1 Mbp of sequenced DNA for tumor samples. Tumor cell PD-L1 IHC was measured (Dako 22C3). Results: Differences in alteration frequencies between PT, MET and LB for selected genes are shown in the Table. TMPRSS2:ERG fusion frequencies were similar between PT and MET (35% vs 33%) but varied between MET sites (27% in BO and ST to 40% in LN). GA in AR were lowest in pre PT (2%) and highest in MET (24% in LU to 50% in LIV). BN had the highest GA/tumor (8) and the most PTEN GA. BRCA2 GA frequency varied from 0% in BN to 15% in LI. Potential predictors of IO response included CDK12 GA (16% in LU) and MSI high status (29% in BN). High PD-L1 expression was found in only two cases (LN) and low PD-L1 expression was relatively uncommon. ERBB2 amplifications were increased in MET compared with PT. RB1 GA were increased in LIV cases. LB GA had a similar increase in AR and TP53 GA to MET and appeared to be a blend of MET site biopsies across alteration frequencies. Conclusions: CGP of PT, MET and LB in PC demonstrates differences most likely associated with exposure to systemic therapies. Differences identified in the MET GA landscape suggest that liquid biopsies may capture a broader range of therapeutic opportunities for PC patients.
| Pre | Post | |||||||
|---|---|---|---|---|---|---|---|---|
| PT | BO | LIV | LU | BN | LN | ST | LB | |
| Cases | 770 | 127 | 34 | 25 | 7 | 205 | 126 | 782 |
| Median age (range) | 64 (39-89+) | 68 (44-89+) | 69 (48-84) | 70 (50-86) | 75 (58-84) | 68 (39-89+) | 68 (44-89+) | 71 (45-89+) |
| GA/sample | 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% | 32% (n = 290) |
| TP53 | 37% | 41% | 56% | 28% | 57% | 50% | 41% | 50% |
| PTEN Copy Number Alterations | 16% | 25% | 24% | 28% | 57% | 33% | 25% | - |
| PTEN Short Variants | 6% | 10% | 15% | 4% | 29% | 7% | 10% | 7% |
| BRCA2 | 9% | 8% | 15% | 8% | 0% | 7% | 8% | 8% |
| ATM | 6% | 6% | 0% | 24% | 0% | 5% | 6% | 15% (n = 290) |
| PIK3CA | 7% | 6% | 3% | 8% | 14% | 6% | 6% | 5% |
| RB1 | 4% | 9% | 30% | 0% | 0% | 5% | 9% | 5% (n-290) |
| CDK12 | 5% | 10% | 0% | 16% | 0% | 5% | 10% | 4% (n = 290) |
| BRAF | 4% | 3% | 6% | 0% | 0% | 3% | 3% | 3% |
| ERBB2 | 0.6% | 5% | 3% | 8% | 0% | 2% | 5% | 1% |
| MSI-High | 2% | 5% | 7% | 0% | 29% | 2% | 5% | 1% (n = 290) |
| Median TMB | 1.3 | 2.5 | 2.5 | 2.5 | 7.5 | 2.5 | 2.5 | - |
| TMB > 10 mut/Mb | 5% | 7% | 9% | 0% | 43% | 4% | 7% | - |
| TMB > 20 mut/Mb | 3% | 4% | 3% | 0% | 29% | 2% | 4% | - |
| PD-L1 IHC Low ( > 1%) Positive | 8% | 3% | 15% | 13% | 0% | 4% | 3% | - |
Disclaimer
This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Abstract Details
Session Type
Poster Session
Session Title
Genitourinary Cancer—Prostate, Testicular, and Penile
Track
Genitourinary Cancer—Prostate, Testicular, and Penile
Sub Track
Prostate Cancer - Advanced Disease
Citation
J Clin Oncol 38: 2020 (suppl; abstr 5534)
DOI
10.1200/JCO.2020.38.15_suppl.5534
Abstract #
5534
Poster Bd #
115
Abstract Disclosures
Similar Abstracts
Abstract
2023 ASCO Annual Meeting
Determinants of widespread metastases and of metastatic tropism in patients with prostate cancer: A genomic analysis of primary and metastatic tumors.
First Author: Edward Christopher Dee
Abstract
2024 ASCO Annual Meeting
Genomic landscape and therapeutic implications in advanced solid cancers: KOSMOS-II (KOrean Precision Medicine Networking Group Study of MOlecular profiling guided therapy based on genomic alterations in advanced Solid tumors, KCSG AL-22-09).
First Author: Heejung Chae
Abstract
2024 ASCO Genitourinary Cancers Symposium
HER2 and PD-L1 immunohistochemistry (IHC) expression, and HER2 genomic alterations: Associations and clinical outcomes for advanced bladder cancer.
First Author: David H Aggen
Abstract
2024 ASCO Annual Meeting
Utilization of genetic and genomic data and correlation to outcomes of treatment with PARP inhibitors in advanced or metastatic castrate-resistant prostate cancer.
First Author: Ted Van Alstyne