Comprehensive genomic profiling (CGP) of metastatic castrate-sensitive prostate cancer (mCSPC) to reveal potential biomarkers and therapeutic targets.

Abstract

198 Background: Docetaxel and androgen receptor (AR) targeted agents have become standard options for mCSPC. CGP data is limited in mCSPC, however has the potential to guide treatment selection. We aimed to establish the feasibility of using CGP to characterize genomic alterations (GAs) in mCSPC. Methods: Patients with mCSPC were prospectively recruited at the Princess Margaret Cancer Centre to the OCTANE trial (NCT02906943), which aims to establish a genomically-characterized and clinically-annotated patient base that can be enrolled into specific research initiatives. Archival tumour specimens (after clinical testing completed) were profiled using next-generation sequencing (NGS) with a custom hybridization capture DNA-based panel (555 genes) or a targeted DNA/RNA amplicon panel (Oncomine Comprehensive Assay v3, 161 driver gene panel). GAs were classified according to the 2017 AMP/ASCO/CAP consensus recommendation. Clinical data were extracted from electronic health records. Results: Since 2016, 17/31 (55%) mCSPC patients who enrolled had sufficient tissue (15 from primary, 1 lymph node, 1 bone) for CGP. All had adenocarcinoma histology, most had high volume (76%) or de novo (71%) mCSPC. Median presenting PSA was 56 µg/L (range 8.4 – 1394). Patients received docetaxel (88%) or abiraterone (12%). Tier I/II GAs consistent with possible benefit from approved or investigational targeted therapies were identified in 14/17 patients (82%). AR pathway GAs (in 29%) were present regardless of prior androgen deprivation therapy or disease volume. DNA damage repair GAs (in 65%) included BRCA2, ATM, PALB2, MLH1/3, CDK12, FANCA, ERCC4, and SPOP. Other GAs involved the cell cycle, mTOR, EGFR, wnt, hedgehog, notch, and epigenetic pathways. Conclusions: In this small cohort, CGP was feasible in the setting of mCSPC for half of the patients. Potentially actionable GAs were identified in over 80% of patients tested. Pending confirmation from larger cohorts, these data support CGP in mCSPC prior to systemic therapy initiation, and highlight its potential role in future biomarker development and trial design in mCSPC.