Publications

Predictive genomic biomarkers in non-metastatic castration resistant prostate cancer (nmCRPC) treated with androgen receptor pathway inhibitors (ARPi)

Predictive genomic biomarkers in non-metastatic castration resistant prostate cancer (nmCRPC) treated with androgen receptor pathway inhibitors (ARPi)

ABSTRACT ONLY| VOLUME 32, SUPPLEMENT 5S647, SEPTEMBER 01, 2021

Predictive genomic biomarkers in non-metastatic castration resistant prostate cancer (nmCRPC) treated with androgen receptor pathway inhibitors (ARPi)

, , , , , , , , , , , , , ,

Background

Although recent trials have demonstrated overall survival (OS) and metastasis free survival (MFS) benefit with the use of ARPi in high-risk nmCRPC, individual treatment outcomes may vary. This retrospective multicentre analysis explores the association between genomic mutations with ARPi treatment outcomes in nmCRPC patients to identify predictive biomarkers.

Methods

In high-risk nmCRPC patients treated with apalutamide, enzalutamide or darolutamide at APCaRI affiliated cancer centres, median MFS, OS, PSA decline ≥ 50% from baseline (PSA50), and second progression free survival (PFS2) were calculated. Next generation gene sequencing (NGS) was performed on archival tumour tissue examining for genomic alterations in 500 genes, including homologous recombination repair (HRR), mismatch repair, tumour suppressor (TS), and PI3K/AKT oncogene (OG) groups. Analysis was conducted using Cox proportional hazards regression using wildtype cases as the reference group, while adjusting for PSA doubling time and presence of pelvic lymph nodes.

Results

Of 32 nmCRPC patients, 25 (78%) were treated with apalutamide, 5 (16%) with darolutamide and 2 (6%) with enzalutamide. 10 patients (31%) had TS/OG mutations (5 PTEN, 8 TP53, 2 PIK3CA), 3 (9%) had HRR gene mutations (2 ATM, 1 BRCA2) and 1 (3%) had 2 MLH1 mutations (microsatellite instability). All 5 patients who received subsequent therapy received abiraterone. Patients with TS/OG mutations had significantly shorter MFS (16.4 mo; HR 5.2; 95% CI 1.4 – 25.7; p = 0.018), PFS2 (22.1 mo; HR 15.4; 95% CI 1.9 – 126.3; p = 0.011) and OS (24.1 mo; HR 8.3; 95% CI 1.2 – 58.8; p = 0.035). Those with HRR mutations had significantly reduced PFS2 (median not reach [NR]; HR 40.4; 95% CI 1.6 – 1034.2; p = 0.025) and OS (NR; HR 21.7; 95% CI 1.1 – 446.1; p = 0.045). 3 (9%) patients did not achieve PSA50, including a patient with 2 MLH1 mutations.

Conclusions

This analysis demonstrates that nmCRPC patient with TS/OG and HRR gene mutations have poor clinical outcomes and may benefit from close follow-up. Our results underline the need for ongoing trials which examine novel targeted therapies (e.g. PARP Inhibitors, AKT inhibitors) in these molecularly defined nmCRPC subgroups.

Its nearly time for the 2018 APCaRI Fall Symposium!

APCaRI will celebrate its 11th research meeting at the Banff Park Lodge, in Banff, Alberta on October 26 to 27, 2018. Please welcome our two invited speakers who will be joining the Symposium this year:

Alison Allan, PhD
Chair, Department of Anatomy & Cell Biology
Associate Professor, Departments of Anatomy & Cell Biology and Oncology
Western University, Ontario CA
and
Melina Cimler, PhD
CEO and Founder
PandiaDx LLC
Frisco, Texas

Previous fall symposia have had over 60 participants participating in this fun and enriching event, including clinicians, scientists, clinical research personnel, trainees, benefactors and representatives of PCa support groups.
Rose Pink Photography was at the 2017 APCaRI Fall Symposium and took these excellent images of the meeting, including the group photo seen in the featured image!

Plan on attending the 2018 Fall symposium to discuss and share ideas and enjoy the beautiful Rockies!
The APCaRI Fall symposium is generously supported by the Alberta Cancer Foundation and its’ donors.

- Perrin Beatty