266P - Clinical application and potential impact of liquid biopsy on the management of Chinese patients with metastatic castration-resistant prostate cancer (mCRPC): A territory-wide prospective analysis

Background

We aimed to report the somatic mutation profiles in Chinese mCRPC patients using blood-based liquid biopsy with next-generation sequencing (NGS), and to investigate associations between NGS results and physician practices in a real-life setting.

Methods

Patients with mCRPC who had clinical, biochemical, or radiologic disease progression and a prostate-specific antigen (PSA) level > 20 ng/mL after first-line systemic therapy were enrolled from 5 centers in Hong Kong. Comprehensive genomic profiling was performed using FoundationOne™ Liquid CDx. NGS results and pre- and post-NGS treatments were analyzed.

Results

This study included 36 patients (median age, 72.5 yr; median PSA, 69.9 ng/mL): 29 (80.6%) had an Eastern Cooperative Oncology Group performance score of 1; one-third had a Gleason score of 9; 28 (77.8%) had symptomatic disease; 7 (19.4%) and 15 (41.7%) received two and three lines of systemic therapies, respectively. Common genomic alterations were found in AR (52.8%), TP53 (44.4%), DNMT3A (33.3%), and BRCA2 (25.0%). Amplification and single-nucleotide variants were detected in 31.6% (6/19) and 47.4% (9/19) of the AR variants, respectively. The most common mutations in homologous recombination repair-related genes were found in BRCA2 (25.0%), CDK12 (19.4%), and ATM (8.3%), at comparable frequencies to those in the PROfound trial (NCT02987543). High microsatellite instability was detected in 2 (5.6%) patients. The overall median tumor mutational burden was 4.0 mut/Mb, 4/9 patients with variant BRCA2 were switched to a poly (ADP-ribose) polymerase (PARP) inhibitor, and all showed clinical benefits. The reasons for not using a PARP inhibitor included poor performance status (n = 2), cost (n = 1), and patient decision (n = 1).

Conclusions

Half of a cohort of Chinese patients with mCRPC who failed first-line therapy had AR mutations. BRCA2 mutations were detected in 9 (25.0%) patients, 4 of whom were switched to a PARP inhibitor and benefited clinically. In a real-life situation, liquid biopsy could potentially impact physician practices as well as patient outcomes.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.