BRCA+ mCRPC patients may face aggressive disease and worse prognosis2-5
~10% of mCRPC patients harbor a BRCA gene mutation6,7
Men with BRCA+ mCRPC may face shortened survival and treatment duration on novel hormonal therapies.8,9
Identifying patients’ mutational status is critical to potentially change the course of the disease pathway in advanced prostate cancer3,8
Prostate cancer–specific survival was halved in mCRPC patients with BRCA2 mutations compared to those without8*
for patients with BRCA2 mutations
for patients without BRCA2 mutations
N=419, P =0.027
Treating with AKEEGA® starts by testing for BRCA1
Is AKEEGA® appropriate for your patient?
Using an FDA-approved diagnostic test, find out if your patient may benefit from AKEEGA®1
Is AKEEGA® appropriate for your patient?
Using an FDA-approved diagnostic test, find out if your patient may benefit from AKEEGA®1
| Tumor tissue or ctDNA testing | Blood or saliva testing | |
|---|---|---|
| Types of tests | Either tumor tissue or ctDNA testing may detect both germline and somatic mutations but is unable to distinguish between the two3 | Both blood and saliva testing can only detect germline mutations but can also inform familial risk and cascade testing10 |
| When to test | National Comprehensive Cancer Network® (NCCN®) recommends somatic testing for all patients with metastatic prostate cancer11 | NCCN recommends germline testing at prostate cancer diagnosis for patients at high risk of certain mutations, such as BRCA1/211 |
Tumor tissue or ctDNA testing
Blood or saliva testing
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend both somatic and germline testing for BRCA1/2 mutations in all patients with metastatic prostate cancer11
- The panel strongly recommends a metastatic biopsy for histologic and molecular evaluation. When unsafe or unfeasible, plasma ctDNA assay is an option, preferably collected during PSA and/or radiographic progression in order to maximize diagnostic yield
- Patients should be informed that tumor testing may uncover germline findings, and confirmatory germline testing may be recommended to inform familial risk
Only AKEEGA® combines the precision of PARP inhibition with an NHT into a dual action tablet1
(PARP inhibitor)
- Blocks PARP-mediated single-strand DNA repair1
- May modulate hormone signaling pathways at the transcriptional level through the AR12
- Selectively causes tumor cell death due to the dependency of DNA repair on the PARP system in BRCA1/2-deficient cells, a phenomenon known as synthetic lethality2,13
PARPi + NHT in BRCA+ mCRPC1
Complementary effects1,13,14
Antitumor activity in BRCA-deficient prostate cancer cells1,13,14
(androgen synthesis inhibitor)
- Abiraterone acetate is converted in vivo to abiraterone, an androgen biosynthesis inhibitor1
- Reduces serum testosterone by inhibiting CYP17 in testicular, adrenal, and prostatic tumor tissues1
- Reduces AR-mediated cancer cell growth1,12
Niraparib and abiraterone acetate (AKEEGA®) is recommended as a Category 1 treatment option in NCCN Guidelines for patients with BRCA+ mCRPC who have not received prior docetaxel or NHT†‡§
Category 1 indicates that based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
- Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate
- Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate
See how AKEEGA® may benefit BRCA+ mCRPC patients
See how AKEEGA®
may benefit
BRCA+ mCRPC patients
AKEEGA® offers 2 drugs under 1 co-pay1
†Niraparib plus abiraterone (combination tablet) is a treatment option for patients with metastatic CRPC and a pathogenic BRCA1 or BRCA2 mutation (germline and/or somatic) who have not yet had treatment in the setting of metastatic CRPC, depending on prior treatment in other disease settings. Use of niraparib/abiraterone for those who have received prior NHT is controversial because a benefit of this combination over use of a PARP inhibitor alone has not been shown in this setting, but responses are likely. The fine particle formulation of abiraterone can be given with single-agent niraparib as a substitute for the combination niraparib/abiraterone tablet (category 2B; other recommended option).11
‡See the NCCN Guidelines for detailed recommendations, including other treatment options.11
§Continue ADT to maintain castrate levels of serum testosterone (<50 ng/dL).11
ADT = androgen deprivation therapy; AR = androgen receptor; BRCA+ = BRCA gene-mutated; BRCAm = BRCA gene mutations; ctDNA = circulating tumor DNA; mCRPC = metastatic castration-resistant prostate cancer; NCCN = National Comprehensive Cancer Network® (NCCN®); NHT = novel hormonal therapy; PARP = poly (ADP-ribose) polymerase; PSA = prostate-specific antigen; T = testosterone.
References:
- AKEEGA® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
- Teyssonneau D, Margot H, Cabart M, et al. Prostate cancer and PARP inhibitors: progress and challenges. J Hematol Oncol 2021;14(1):51.
- 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.
- 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.
- Messina C, Cattrini C, Soldato D, et al. BRCA mutations in prostate cancer: prognostic and predictive implications. J Oncol. 2020;2020:4986365.
- 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(4):977-986.
- 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-December 2, 2022; San Diego, CA.
- 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.
- 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.
- Cresta Morgado P, Mateo J. Clinical implications of homologous recombination repair mutations in prostate cancer. Prostate. 2022;82 Suppl 1:S45‐S59.
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V.4.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed September 7, 2023. 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.
- Schiewer MJ, Goodwin JF, Han S, et al. Dual roles of PARP-1 promote cancer growth and progression. Cancer Discovery. 2012;2(12):1134-1149.
- Asim M, Tarish F, Zecchini HI, et al. Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer. Nat Commun. 2017;8(1):374.
- Li L, Karanika S, Yang G, et al. Androgen receptor inhibitor-induced “BRCAness” and PARP inhibition are synthetically lethal for castration-resistant prostate cancer. Sci Signal. 2017;10(480):eaam7479.
