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MEN WITH METASTATIC PROSTATE CANCER AREN't ALL THE SAME

HRR mutations, including BRCA1/2, in your patients with metastatic prostate cancer can mean more aggressive disease and poorer prognosis, posing a greater need for precision medicine. These mutations often go unidentified in the first line, but early genetic testing makes it easier to uncover driver mutations in these patients to help inform their treatment plan.1-5

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BRCA1/2 MUTATIONS CAN DRIVE AGGRESSIVE mCRPC

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BRCA1 and 2 mutations are among the most commonly occurring actionable alterations within mCRPC, with a combined rate of ~10%.5-10

Both germline and somatic BRCA1/2 mutations can be used to identify patients with potentially poorer prognosis, including shorter time to progression and worse overall survival.2,5,11,12

BIOMARKER TESTING CAN HELP REVEAL PRECISION MEDICINE OPTIONS FOR MEN WITH METASTATIC PROSTATE CANCER2,8

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PRECISION MEDICINE CAN HELP OPTIMIZE OUTCOMES FOR BRCA+ PATIENTS WITH mCRPC4

mCRPC patients with HRR mutations, including BRCA1/2, can quickly develop resistance to a first-line novel hormonal therapy, the current standard of care.13,14

Men with BRCA2 mutations may face shorter prostate cancer-specific survival than those without11

Prostate cancer-specific survival (months) 17.4 months 33.2 months P =0.027 0 5 10 15 20 25 30 35 Patients with BRCA2 mutations Patients without BRCA2 mutations Patients with BRCA2 mutations Patients without BRCA2 mutations 0 5 10 15 20 25 30 35 17.4 months 33.2 months P =0.027 Prostate cancer-specific survival (months)

In a multicenter prospective cohort study of 419 men with mCRPC, prostate cancer-specific survival was halved in those with germline BRCA2 mutations (17.4 vs 33.2 months; P=0.027).11

SOMATIC AND GERMLINE BRCA1/2 MUTATIONS ARE VULNERABLE TO PARP INHIBITION THROUGH SYNTHETIC LETHALITY8

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TEST AT METASTATIC DIAGNOSIS TO TREAT WITH PRECISION15

It is now recognized that biomarker testing may help create individualized treatment strategies in prostate cancer. Testing to identify somatic and germline BRCA gene mutations may be informative for guiding treatment decisions and determining clinical trial eligibility.15,16

NCCN CLINICAL PRACTICE GUIDELINES IN ONCOLOGY (NCCN GUIDELINES®) RECOMMENDED

The NCCN Guidelines® recommend both somatic and germline testing for HRR mutations, including BRCA1/2, in all patients with metastatic prostate cancer.15

38 Percent

Although PARP inhibitors have demonstrated efficacy among patients with HRR mutations such as BRCA1/2, only ~38% of mCRPC patients undergo biomarker testing for these mutations.4

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    Germline mutations are inherited pathogenic variants that are present in all cells of the body. These mutations can be identified via liquid assay biomarker testing (blood or saliva)8,17

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    Somatic, or acquired, mutations can only be identified via tumor-based testing (tumor sample or ctDNA). Tumor-based testing does not distinguish between germline and somatic mutations8,17

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    Follow-up germline testing and genetic counseling are recommended to identify possible implications for inherited cancer predisposition for any patients found to have clinically meaningful mutations via tumor-based testing17

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    Biomarker testing may benefit a patient’s biological family members. Those harboring germline BRCA1 or 2 mutations are 3.4 or 8.6 times more likely, respectively, to develop prostate cancer than those without either mutation, and are also at greater risk of developing breast or ovarian cancer12,18

BIOMARKER TESTING AT METASTATIC DIAGNOSIS IS CRUCIAL TO HELP OPTIMIZE TREATMENT OUTCOMES3

Biomarker testing
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Explore the differences between tumor tissue, ctDNA, blood, and saliva testing and view laboratory options that offer BRCA testing.

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ctDNA, circulating tumor DNA; HRR, homologous recombination repair; mCRPC, metastatic castration-resistant prostate cancer; NCCN, National Comprehensive Cancer Network® (NCCN®); OS‍, overall survival; PARP, poly (ADP-ribose) polymerase.

References: 1. Teyssonneau D, Margot H, Cabart M, et al. Prostate cancer and PARP inhibitors: progress and challenges. J Hematol Oncol. 2021;14(1):51. 2. Scott RJ, Mehta A, Macedo GS, et al. Genetic testing for homologous recombination repair (HRR) in metastatic castration-resistant prostate cancer (mCRPC): challenges and solutions. Oncotarget. 2021;12(16):1600-1614. 3. Giri VN, Morgan TM, Morris DS, et al. Genetic testing in prostate cancer management: considerations informing primary care. CA Cancer J Clin. 2022;0:1‐12. 4. Leith A, Ribbands A, Kim J, et al. Real-world homologous recombination repair mutation testing in metastatic castration-resistant prostate cancer in the USA, Europe and Japan. Future Oncol. 2022;18(8):937-951. 5. Messina C, Cattrini C, Soldato D, et al. BRCA mutations in prostate cancer: prognostic and predictive implications. J Oncol. 2020;4986365. 6. Shah S, Rachmat R, Enyioma S, et al. BRCA mutations in prostate cancer: assessment, implications and treatment considerations. Int J Mol Sci. 2021; 22(23):12628. 7. Robinson D, Van Allen YM, Wu Y, et al. Integrative clinical genomics of advanced prostate cancer. Cell. 2015;161(5):1215-1228. 8. Shore N, Ionescu-Ittu R, Yang L, et al. Real-world genetic testing patterns in metastatic castration-resistant prostate cancer. Future Oncol. 2021;17(22):2907-2921. 9. Shore N, Oliver L, Shui I, et al. Systematic literature review of the epidemiology of advanced prostate cancer and associated homologous recombination repair gene alterations. J Urol. 2021;205:977-986. 10. George DJ, Khilfeh I, Rossi C, et al. Real-world prevalence of select homologous recombination repair (HRR) alterations in patients with metastatic castration-resistant prostate cancer (mCRPC). Poster presented at: the 23rd Annual Meeting of the Society of Urologic Oncology; November 30-Decemeber 2, 2022; San Diego, CA. 11. Castro E, Romero-Laorden N, Del Pozo A, et al. PROREPAIR-B: a prospective cohort study of the impact of germline DNA repair mutations on the outcomes of patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2019;37(6):490-503. 12. Castro E, Goh C, Olmos D, et al. Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer. J Clin Oncol. 2013;31(14):1748-1757. 13. Clarke N, Wiechno P, Alekseev B, et al. Olaparib combined with abiraterone in patients with metastatic castration- resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2018;19(7):975-986. 14. Annala M, Struss WJ, Warner EW, et al. Treatment outcomes and tumor loss of heterozygosity in germline DNA repair- deficient prostate cancer. Eur Urol. 2017;72(1):34-42. 15. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V.1.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed January 23, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 16. Mateo J, Carreira S, Sandhu S, et al. DNA-repair defects and olaparib in metastatic prostate cancer. N Engl J Med. 2015;373(18):1697-1708. 17. Cimadamore A, Lopez-Beltran A, Massari F, et al. Germline and somatic mutations in prostate cancer: focus on defective DNA repair, PARP inhibitors and immunotherapy. Future Oncol. 2020;16(5)75-80. 18. Giri V, Beebe-Dimmer JL. Familial prostate cancer. Semin Oncol. 2016;43(5):560‐565. 19. Carter BH, Helfand B, Mamawala M, et al. Germline mutations in ATM and BRCA1/2 are associated with grade reclassification in men on active surveillance for prostate cancer. Eur Urol. 2019;75(5):743‐749.

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