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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)

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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.

Lifestyle Management Program in Alberta – TrueNTH

The TrueNTH (pronounced True North) Lifestyle Management (LM) Program is part of the Global TrueNTH network funded by Movember (in partnership with Prostate Cancer Canada nationally). TrueNTH LM aims to improve the survivorship experience for men living with prostate cancer through physical activity, nutrition, and stress-reduction resources (programs and educational materials).

TrueNTH LM includes a free 12-week physical activity and yoga program with classes designed specifically to address the health and treatment related concerns for men living with prostate cancer. Men can also access a comprehensive online portal with tools, education, and home-based programming for help with staying active, reducing stress, and maintaining a proper diet.

In Calgary, TrueNTH LM has partnered with City of Calgary Recreation to offer programs at four different locations throughout the city. Registration is ongoing for men. In Edmonton, the Cancer Rehabilitation Clinic at the University of Alberta will be hosting a TrueNTH LM program starting in January 2016. Future programs will be announced as they become available. Men living in rural Alberta are able to join an online-based program at lifestyle.truenth.ca

All men who have been previously diagnosed with prostate cancer regardless of when they were diagnosed or what treatment they received can join the TrueNTH LM online portal or join a community program. Each person will undergo an initial health screening to ensure physical activity is safe.

For more information or to register, phone the Health and Wellness Lab in Calgary at .

Letter for participants

- Nicole Culos-Reed