The utility of genomic profiling in prostate cancer: Insights from a phase I setting.

Abstract

e17062 Background: Prostate cancer, one of the most frequent cancers among men, has increasingly benefited from precision oncology during the last decade, leading to improved clinical outcomes. Here, we report the impact of comprehensive genomic profiling in a substantial cohort of 174 patients with advanced prostate cancer at the Phase I Unit, Department of Oncology, Rigshospitalet, Denmark. Methods: A prospective, single-center, single-arm open label study (NCT02290522) was conducted, enrolling patients with advanced cancer referred to the Phase I Unit. Fresh tumor tissue was obtained for whole genome or exome sequencing, RNA sequencing, and SNP array analysis. In cases where fresh tumor tissue was unavailable, archived formalin-fixed paraffin-embedded tumor tissue or circulating tumor DNA extracted from plasma were obtained. Each individual genomic report was reviewed and discussed by a multidisciplinary tumor board dedicated to precision medicine. Actionable alterations were classified retrospectively (Nov2024) according to the ESMO Scale for the Clinical Actionability of Molecular Targets (ESCAT). When possible, patients were treated with a regimen matched to the genomic profile. Results: Between April 2013 and December 2021, a total of 174 patients with metastatic prostate cancer were enrolled. Genomic profiles were obtained in 161 patients (93%). At least one actionable target was identified in 61 patients (38%) with a total of 79 actionable alterations including BRCA1/2 alterations (N=20, 25%), ATM mutations (N=18, 23%) and AR mutations (N=13, 16%). Overall, 25 patients, representing 41% of the patients with an actionable target, were treated with genomic-guided treatment and 2 patients were treated with more than one line: 21 actionable targets were classified as ESCAT I/II and 6 as ESCAT III/IV. The overall response rate was 30% (CI95%: 0.12 – 0.47). The median progression-free survival (PFS) and a median overall survival (OS) were 4.7 months (CI95%: 2 – 8.75) and 13.5 months (CI95%: 9.51 – 23.3), respectively. Conclusions: This study emphasizes the clinical value of genomic profiling in patients with prostate cancer by identifying actionable targets, enabling genomic-guided treatment, and contributing to improved clinical outcomes.