Special Report

Department of Medical Oncology, Ankara University School of Medicine, Ankara, Turkey

Ankara University Cancer Research Institute, Ankara, Turkey

Search for more papers by this author

Yüksel Ürün

*Author for correspondence: Tel.: +90 312 595 7112;

E-mail Address: yuksel.urun@ankara.edu.tr

https://orcid.org/0000-0002-9152-9887

Department of Medical Oncology, Ankara University School of Medicine, Ankara, Turkey

Ankara University Cancer Research Institute, Ankara, Turkey

Search for more papers by this author

Published Online:11 Dec 2023https://doi.org/10.2217/fon-2023-0550

View article

Abstract

The treatment landscape for castration-resistant prostate cancer (mCRPC) is undergoing significant advancements, particularly with the emergence of poly(ADP-ribose) polymerase inhibitors and their recent US FDA authorizations. The combination of olaparib with abiraterone and prednisone/prednisolone has gained approval for mCRPC patients harboring confirmed BRCA mutations. Subsequently, talazoparib in combination with enzalutamide was approved for patients with mutations in homologous recombination repair genes. Nevertheless, emerging evidence suggests that these treatments may confer benefits irrespective of specific biomarkers. While the understanding of biomarkers in therapy selection for mCRPC is expanding, further data are warranted to provide comprehensive elucidation for guiding clinical practice.

Tweetable abstract

How to determine the MAGNITUDE of benefit from poly(ADP-ribose) polymerase inhibitors? Ongoing debate on the utilization of biomarkers.

Keywords:

Papers of special note have been highlighted as: • of interest

References

1. Sung H, Ferlay J, Siegel RL et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71(3), 209–249 (2021).
MedlineGoogle Scholar
2. Gillessen S, Bossi A, Davis ID et al. Management of patients with advanced prostate cancer-metastatic and/or castration-resistant prostate cancer: Report of the Advanced Prostate Cancer Consensus Conference (APCCC) 2022. Eur. J. Cancer 185, 178–215 (2023).
MedlineGoogle Scholar
3. Abida W, Armenia J, Gopalan A et al. Prospective genomic profiling of prostate cancer across disease states reveals germline and somatic alterations that may affect clinical decision making. JCO Precis. Oncol. 1, 1–16 (2017).
Google Scholar
4. Robinson D, Van Allen EM, Wu YM et al. Integrative clinical genomics of advanced prostate cancer. Cell 161(5), 1215–1228 (2015).
Medline CASGoogle Scholar
5. Patel AG, Sarkaria JN, Kaufmann SH. Nonhomologous end joining drives poly(ADP-ribose) polymerase (PARP) inhibitor lethality in homologous recombination-deficient cells. Proc. Natl Acad. Sci. USA 108(8), 3406–3411 (2011).
Medline CASGoogle Scholar
6. Teyssonneau D, Margot H, Cabart M et al. Prostate cancer and PARP inhibitors: progress and challenges. J. Hematol. Oncol. 14(1), 51 (2021).
Medline CASGoogle Scholar
7. Abida W, Patnaik A, Campbell D et al. Rucaparib in men with metastatic castration-resistant prostate cancer harboring a BRCA1 or BRCA2 gene alteration. J. Clin. Oncol. 38(32), 3763 (2020).
Medline CASGoogle Scholar
8. De Bono J, Mateo J, Fizazi K et al. Olaparib for metastatic castration-resistant prostate cancer. N. Engl. J. Med. 382(22), 2091–2102 (2020).
MedlineGoogle Scholar
9. 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 doi:10.1016/S0140-6736(23)01055-3 (2023) (Epub ahead of print). • The trial showed the most significant improvement in progression-free survival by the addition of poly(ADP-ribose) polymerase inhibition to androgen receptor signaling inhibition.
Google Scholar
10. Chi KN, Rathkopf D, Smith MR et al. Niraparib and abiraterone acetate for metastatic castration-resistant prostate cancer. J. Clin.Oncol. 41(18), 3339–3351 (2023). • Pivotal phase III trial of niraparib and abirateron combination
Medline CASGoogle Scholar
11. 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. 19(7), 975–986 (2018).
Medline CASGoogle Scholar
12. Clarke NW, Armstrong AJ, Thiery-Vuillemin A et al. Abiraterone and olaparib for metastatic castration-resistant prostate cancer. NEJM Evid. 1(9), (2022). • Important phase III study of olaparib and abiraterone combination, leading to US FDA approval.
MedlineGoogle Scholar
13. Clarke NW, Armstrong AJ, Thiery-Vuillemin A et al. Final overall survival (OS) in PROpel: abiraterone (abi) and olaparib (ola) versus abiraterone and placebo (pbo) as first-line (1L) therapy for metastatic castration-resistant prostate cancer (mCRPC). J. Clin. Oncol. 41(Suppl. 6), LBA16–LBA16 (2023).
Google Scholar
14. Schiewer MJ, Goodwin JF, Han S et al. Dual roles of PARP-1 promote cancer growth and progression. Cancer Discov. 2(12), 1134–1149 (2012).
Medline CASGoogle Scholar
15. Polkinghorn WR, Parker JS, Lee MX et al. Androgen receptor signaling regulates DNA repair in prostate cancers. Cancer Discov. 3(11), 1245–1253 (2013).
Medline CASGoogle Scholar
16. 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. Sig. 10(480), eaam7479 (2017).
MedlineGoogle Scholar
17. Li Y, Zhao Z, Ai L et al. Discovering a qualitative transcriptional signature of homologous recombination defectiveness for prostate cancer. iScience 24(10), 103135 (2021).
Medline CASGoogle Scholar
18. Lotan TL, Kaur HB, Salles DC et al. Homologous recombination deficiency (HRD) score in germline BRCA2- versus ATM-altered prostate cancer. Mod. Pathol. 34(6), 1185–1193 (2021).
Medline CASGoogle Scholar
19. Mateo J, Carreira S, Sandhu S et al. DNA-repair defects and olaparib in metastatic prostate cancer. N. Engl. J. Med. 373(18), 1697–1708 (2015).
Medline CASGoogle Scholar
20. Mateo J, Porta N, Bianchini D et al. Olaparib in patients with metastatic castration-resistant prostate cancer with DNA repair gene aberrations (TOPARP-B): a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 21(1), 162–174 (2020).
Medline CASGoogle Scholar
21. Hussain MHA, 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. 40(Suppl. 16), S5018–S5018 (2022).
Google Scholar
22. Matsubara N, De Bono J, Olmos D et al. Olaparib efficacy in patients with metastatic castration-resistant prostate cancer and BRCA1, BRCA2, or ATM alterations identified by testing circulating tumor DNA. Clin. Cancer Res. 29(1), 92–99 (2023).
Medline CASGoogle Scholar
23. 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. 26(11), 2487–2496 (2020).
Medline CASGoogle Scholar
24. Fizazi K, Piulats JM, Reaume MN et al. Rucaparib or physician's choice in metastatic prostate cancer. N. Engl. J. Med. 388(8), 719–732 (2023). • Recent pivotal trial investigating the efficacy of rucaparib and androgen receptor signaling inhibitor combination therapy.
Medline CASGoogle Scholar
25. Smith MR, Scher HI, Sandhu S et al. Niraparib in patients with metastatic castration-resistant prostate cancer and DNA repair gene defects (GALAHAD): a multicentre, open-label, phase 2 trial. Lancet Oncol. 23(3), 362–373 (2022).
Medline CASGoogle Scholar
26. Chi KN, Fleshner N, Chiuri VE et al. Niraparib with abiraterone acetate and prednisone for metastatic castration-resistant prostate cancer: phase II QUEST study results. Oncologist 28(5), e309–e312 (2023).
MedlineGoogle Scholar
27. Sandhu S, Attard G, Olmos D et al. Gene-by-gene analysis in the MAGNITUDE study of niraparib (NIRA) with abiraterone acetate and prednisone (AAP) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations. J. Clin. Oncol. 40(Suppl. 16), S5020–S5020 (2022).
Google Scholar
28. De Bono JS, Mehra N, Scagliotti GV et al. Talazoparib monotherapy in metastatic castration-resistant prostate cancer with DNA repair alterations (TALAPRO-1): an open-label, phase 2 trial. Lancet Oncol. 22(9), 1250–1264 (2021).
MedlineGoogle Scholar

Vol. 19, No. 39

Metrics

Downloaded 108 times

History

Received 26 June 2023

Accepted 10 November 2023

Published online 11 December 2023

Published in print December 2023

Information

Keywords

Author contributions

Both authors participated in development of the manuscript, contributed to revising the draft manuscript and read and approved the final manuscript.

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Competing interests disclosure

Advisory boards: Y Ürün has served on the advisory board for Abdi-İbrahim, Astellas, AstraZeneca, Bristol Myers Squibb, Eczacıbaşı, Gilead, Janssen, Merck, Novartis, Pfizer and Roche. Consultancy: Y Ürün received honoraria or has served as a consultant for Abdi-İbrahim, Astellas, Bristol Myers Squibb, Eczacıbaşı, Janssen, Merck, Novartis, Pfizer and Roche. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

PDF download

Determining magnitude of benefit from poly(ADP-ribose) polymerase inhibitors in prostate cancer

Abstract

Tweetable abstract

References