South Central Section of the AUA 2022

SCS AUA 2022: Rapid Genomic Profiling To Identify Actionable Variants In Advanced Prostate Cancer

(UroToday.com) Genomic profiling of tumors provides biologic insights that potentially impact selection of treatment regimes. In this descriptive clinical utility study, they profiled prostate cancer (PCa) samples using the Oncotype MAPTM pan-cancer tissue test to identify therapeutic variants.

 

The authors performed a retrospective cohort study where 228 advanced PCa samples were submitted for Oncotype MAP testing. This 257-gene panel test utilizes DNA extracted from tumor tissue to identify single nucleotide variants, indels, copy number alterations, and select structural variants/fusions by next-generation sequencing (NGS). The test also assesses tumor mutational burden and microsatellite instability. In addition, a custom immunohistochemical panel evaluates expression of various proteins, including PD-L1. Result were evaluated using a proprietary knowledge base of genomic and proteomic data that includes United States Federal Drug Administration (FDA) approvals, National Comprehensive Cancer Network (NCCN®) recommendations, and published biomarker data for potentially targetable alterations. Eligibility for ongoing clinical trials is determined using the National Cancer Institute (NCI) database.

Of the 228 samples, 203 met minimum tissue requirements (3mm2 and ≥15% tumor cellularity) and 201 were submitted for next-generation sequencing (NGS). Of these, 168 (84%) were successfully sequenced. Successful sequencing declined with sample age, from 94% in samples less than 1-month-old to 62% in samples 5-20 years old. Median turnaround time was 5 calendar days (interquartile range 4-6 days). Tumor mutational burden was high (≥10 mutations/Mb) in 15 samples (8%) and microsatellite instability was high in 8 (all of which were also high tumor mutational burden). PD-L1 expression (≥1%) was observed in 22/168 (13%) samples, with 6 (3%) showing high expression (≥50%). In a preliminary analysis, therapy-targetable genomic variants were identified in 46% (77/168) of samples (level 1 or 2 evidence) with 90% (69/77) recommended for an oral therapy. Including clinical trials, 72% (121/168) of samples had a clinically actionable genomic variant. Twenty percent (33/168) of samples had at least one clinically significant variant in a homologous recombination repair gene, about half of which (17/33) were in BRCA1/2, consistent with PARP inhibitor use indications.

The Oncotype MAP Pan-Cancer Tissue test identified clinically actionable genomic variants in 72% of PCa samples. The assay’s ability to rapidly identify actionable mutations in the majority of patients and high degree of successful sequencing are important attributes that support management of patients with advanced PCa. We are in the age of precision-based medicine and further long-term results are needed to understand real-world application along with economic considerations.

Presented by: Steven Canfield, MD, Associate Professor and Chair of the Division of Urology at McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth)

Written by: Stephen B. Williams, MD, MBA, MS @SWilliams_MD on Twitter during the South Central Section American Urological Association Annual Meeting, September 6-10, 2022, Coronado, CA


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