TY - JOUR
T1 - PARP inhibitors as a new therapeutic option in metastatic prostate cancer
T2 - a systematic review
AU - Ratta, Raffaele
AU - Guida, Annalisa
AU - Scotté, Florian
AU - Neuzillet, Yann
AU - Teillet, Asmahane Benmaziane
AU - Lebret, Thierry
AU - Beuzeboc, Philippe
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Background: A great number of DNA-damage repair (DDR) pathways have been recognized to be frequently dysregulated in advanced stages of prostate cancer. DNA-repair defects in prostate cancer represents a clinically relevant disease subset. Tumors whose ability to repair double-strand DNA breaks by homologous recombination is compromised, are highly sensitive to blockade of the repair of DNA single-strand breaks via the inhibition of the enzyme poly(ADP) ribose polymerase (PARP). Methods: A systematic review of the literature has been conducted in January 2020 using PubMed Medline database in line with the recommendations from the PRISMA guidelines. The following string terms were used for searching clinical trial articles: castration resistant OR castrate resistance OR castration refractory AND prostate cancer AND PARP OR poly(ADP-ribose) polymerase inhibitor OR DNA-repair OR homologous recombination repair. On-going clinical trials with olaparib, niraparib, talazoparib, veliparib, and rucaparib in mCRPC were searched on the clinicalTrials.gov website. Results: From this research 176 articles were identified. After title screening and abstract reading, five papers and four abstract were considered for the systematic review. Thirty-two clinical trials were also identified: from these 16 trials which did not include mCRPC patients or only prostate cancer patients, trials not yet recruiting and trials including radio-metabolic treatments were excluded. Sixteen trials were included and discussed in the paper. Conclusions: Olaparib has been the first agent showing a benefit in terms of rPFS and ORR alone or in combination with abiraterone plus prednisone in patients with DDR deficiency prostate cancer. Also rucaparib showed a benefit in terms of PSA response rate and ORR in patients with BRCA2 and BRCA1 mutation in a phase-II study. Other phase-III clinical trials are evaluating niraparib and talazoparib, alone or in combination with AR signaling inhibitors.
AB - Background: A great number of DNA-damage repair (DDR) pathways have been recognized to be frequently dysregulated in advanced stages of prostate cancer. DNA-repair defects in prostate cancer represents a clinically relevant disease subset. Tumors whose ability to repair double-strand DNA breaks by homologous recombination is compromised, are highly sensitive to blockade of the repair of DNA single-strand breaks via the inhibition of the enzyme poly(ADP) ribose polymerase (PARP). Methods: A systematic review of the literature has been conducted in January 2020 using PubMed Medline database in line with the recommendations from the PRISMA guidelines. The following string terms were used for searching clinical trial articles: castration resistant OR castrate resistance OR castration refractory AND prostate cancer AND PARP OR poly(ADP-ribose) polymerase inhibitor OR DNA-repair OR homologous recombination repair. On-going clinical trials with olaparib, niraparib, talazoparib, veliparib, and rucaparib in mCRPC were searched on the clinicalTrials.gov website. Results: From this research 176 articles were identified. After title screening and abstract reading, five papers and four abstract were considered for the systematic review. Thirty-two clinical trials were also identified: from these 16 trials which did not include mCRPC patients or only prostate cancer patients, trials not yet recruiting and trials including radio-metabolic treatments were excluded. Sixteen trials were included and discussed in the paper. Conclusions: Olaparib has been the first agent showing a benefit in terms of rPFS and ORR alone or in combination with abiraterone plus prednisone in patients with DDR deficiency prostate cancer. Also rucaparib showed a benefit in terms of PSA response rate and ORR in patients with BRCA2 and BRCA1 mutation in a phase-II study. Other phase-III clinical trials are evaluating niraparib and talazoparib, alone or in combination with AR signaling inhibitors.
UR - http://www.scopus.com/inward/record.url?scp=85085111792&partnerID=8YFLogxK
U2 - 10.1038/s41391-020-0233-3
DO - 10.1038/s41391-020-0233-3
M3 - Review article
C2 - 32367009
AN - SCOPUS:85085111792
SN - 1365-7852
VL - 23
SP - 549
EP - 560
JO - Prostate Cancer and Prostatic Diseases
JF - Prostate Cancer and Prostatic Diseases
IS - 4
ER -