Management of advanced prostate cancer with specific germline or somatic homologous recombination repair deficiency

Agents	HRR deficiencies	Indications and timing for use in metastatic CRPC after disease progression	Studies
Olaparib	ATM, BRCA1, BRCA2, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L	Prior ARPI	PROfound^[1]
Rucaparib	BRCA1/2	Prior ARPI and taxane	TRITON2^[2]
Talazoparib and enzalutamide	ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C	No prior ARPI	TALAPRO-2^[3]
Olaparib and abiraterone	BRCA1/2	No prior ARPI	PROPEL, BRCAAWAY^[4,5]
Niraparib and abiraterone	BRCA1/2	No prior ARPI	MAGNITUDE^[6]

ARPI: androgen receptor pathway inhibitor; CRPC: castration-resistant prostate cancer; HRR: homologous recombination repair.

References:

de Bono J, Mateo J, Fizazi K, et al. Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med 2020; 382:2091.
Abida W, Campbell D, Patnaik A, et al. Non-BRCA DNA damage repair gene alterations and response to the PARP inhibitor rucaparib in metastatic castration-resistant prostate cancer: Analysis from the phase II TRITON2 study. Clin Cancer Res 2020; 26:2487.
Agarwal N, Azad AA, Carles J, et al. Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): A randomised, placebo-controlled, phase 3 trial. Lancet 2023; 402:291.
Clarke NW, Armstrong AJ, Thiery-Vuillemin A, et al. Abiraterone and olaparib for metastatic castration-resistant prostate cancer. NEJM Evid 2022; 1:EVIDoa2200043.
Hussain MH, Kocherginsky M, Agarwal N, et al. BRCAAWAY: A randomized phase 2 trial of abiraterone, olaparib, or abiraterone + olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC) with DNA repair defects. J Clin Oncol 2022; 40:ASCO #5018.
Chi KN, Rathkopf D, Smith MR, et al. Niraparib and abiraterone acetate for metastatic castration-resistant prostate cancer. J Clin Oncol 2023; 41:3339.

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