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Attend this session at the
2019 ASCO Annual Meeting!


Session: Genitourinary (Prostate) Cancer

Type: Poster Session

Time: Saturday June 1, 1:15 PM to 4:15 PM

Location: Hall A

Genomic landscape of metastatic hormone sensitive prostate cancer (mHSPC) vs. metastatic castration-refractory prostate cancer (mCRPC) by circulating tumor DNA (ctDNA).

Sub-category:
Advanced Disease

Category:
Genitourinary (Prostate) Cancer

Meeting:
2019 ASCO Annual Meeting

Abstract No:
5043

Poster Board Number:
Poster Session (Board #155)

Citation:
J Clin Oncol 37, 2019 (suppl; abstr 5043)

Author(s): Andrew W Hahn, Edwin Lin, John Esther, Neysi Anderson, Nityam Rathi, Mark Yandell, Benjamin Louis Maughan, Neeraj Agarwal; University of Utah Hunstman Cancer Institute, Salt Lake City, UT; University of Utah/Huntsman Cancer Institute, Salt Lake City, UT; University of Utah, Salt Lake City, UT; University of Utah Huntsman Cancer Institute, Salt Lake City, UT; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD

Abstract Disclosures

Abstract:

Background: mCRPC carries a poor prognosis, and targeted therapies have had minimal success in mCRPC. Novel genomic targets could improve drug development. To date, large ctDNA studies in metastatic prostate cancer have been descriptive with limited or no clinical annotation. Herein, we hypothesize that profiles of genomic alterations (GAs) in ctDNA not only differ significantly between, but can also be used to predict mCRPC vs. mHSPC. These findings could help identify new drug targets for mCRPC treatment. Methods: Men with mHSPC or mCRPC who underwent NGS of ctDNA using G360 (Guardant Health Inc.) at the Huntsman Cancer Institute were included. Men were classified as mCRPC or mHSPC (patients with current or no prior ADT). G360 detects somatic mutations in selected exons of 73 genes, amplifications in 18 genes, and selected fusions in 6 genes. Two-sided students t-test was used to compare the %cfDNA and total GAs. The Chi squared test was used to compare the frequency of each GA. Machine learning (ML) algorithms were trained on GAs and benchmarked by cross-validated performance. GAs contributing to mCRPC vs. mHSPC classification were measured by ML feature importance (e.g. odds ratios, regression coefficients). Results: Of the 259 men included, 119 men had mHSPC and 140 had mCRPC. Men with mCRPC had more GAs (4.5 vs. 1.86, p<0.0001) and higher %cfDNA (9.56% vs. 5.02%, p=0.02). In mHSPC, there was no significant difference in the number of GAs or %cfDNA between men on ADT and those who hadn’t yet started ADT. ML algorithms used GAs to predict mCRPC with 78.1% sensitivity, 64.0% specificity, 76.7% PPV, 65.1% NPV, and 70.3% overall accuracy. mCRPC was enriched with GAs in AR, ARID1A, BRAF, BRCA2, CCNE1, CTNNB1, EGFR, FGFR1, KIT, MET, MYC, PDGFRB, PIK3CA, and TP53. Of note, many of these genes are involved in MAP/ERK signaling. Conclusions: Men with mCRPC have more GAs, higher %cfDNA, and enrichment of GAs in the MAP/ERK pathway compared to men with mHSPC. The distinct GAs seen in mCRPC represent novel therapeutic targets, especially in the MAP/ERK pathway. We also show that machine learning can differentiate mHSPC and mCRPC based on GAs detected in ctDNA.

 
Other Abstracts in this Sub-Category:

 

1. Overall survival (OS) results of a phase III randomized trial of standard-of-care therapy with or without enzalutamide for metastatic hormone-sensitive prostate cancer (mHSPC): ENZAMET (ANZUP 1304), an ANZUP-led international cooperative group trial.

Meeting: 2019 ASCO Annual Meeting Abstract No: LBA2 First Author: Christopher Sweeney
Category: Genitourinary (Prostate) Cancer - Advanced Disease

 

2. Impact of darolutamide (DARO) on pain and quality of life (QoL) in patients (Pts) with nonmetastatic castrate-resistant prostate cancer (nmCRPC).

Meeting: 2019 ASCO Annual Meeting Abstract No: 5000 First Author: Karim Fizazi
Category: Genitourinary (Prostate) Cancer - Advanced Disease

 

3. Interest of short hormonotherapy (HT) associated with radiotherapy (RT) as salvage treatment for metastatic free survival (MFS) after radical prostatectomy (RP): Update at 9 years of the GETUG-AFU 16 phase III randomized trial (NCT00423475).

Meeting: 2019 ASCO Annual Meeting Abstract No: 5001 First Author: Christian Carrie
Category: Genitourinary (Prostate) Cancer - Advanced Disease

 

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