Durable benefit from poly(ADP-ribose) polymerase inhibitors in metastatic prostate cancer in routine practice: biomarker associations and implications for optimal clinical next-generation sequencing testing DOI Creative Commons

Daniel Triner,

Ryon P. Graf, Russell W. Madison

et al.

ESMO Open, Journal Year: 2024, Volume and Issue: 9(9), P. 103684 - 103684

Published: Sept. 1, 2024

Language: Английский

Management of Patients with Advanced Prostate Cancer. Report from the 2024 Advanced Prostate Cancer Consensus Conference (APCCC) DOI Creative Commons
Silke Gillessen, Fabio Turco, Ian D. Davis

et al.

European Urology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Innovations have improved outcomes in advanced prostate cancer (PC). Nonetheless, we continue to lack high-level evidence on a variety of topics that greatly impact daily practice. The 2024 Advanced Prostate Cancer Consensus Conference (APCCC) surveyed experts key questions clinical management order supplement evidence-based guidelines. Here present voting results for from APCCC 2024.

Language: Английский

Citations

16

Heterogeneity of the Treatment Effect with PARP Inhibitors in Metastatic Castration-resistant Prostate Cancer: A Living Interactive Systematic Review and Meta-analysis DOI
Syed Arsalan Ahmed Naqvi, Irbaz Bin Riaz,

Arifa Bibi

et al.

European Urology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

2

Abiraterone, Olaparib, or Abiraterone + Olaparib in First-line Metastatic Castration-Resistant Prostate Cancer with DNA Repair Defects (BRCAAway) DOI
Maha Hussain,

Masha Kocherginsky,

Neeraj Agarwal

et al.

Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 30(19), P. 4318 - 4328

Published: Aug. 8, 2024

Abstract Purpose: Deleterious germline/somatic homologous recombination repair mutations (HRRm) are present in ∼25% of patients with metastatic castration-resistant prostate cancer (mCRPC). Preclinically, poly(ADP-ribose) polymerase (PARP) inhibition demonstrated synergism androgen receptor pathway (ARP)–targeted therapy. This trial evaluated the efficacy ARP inhibitor versus PARP their combination as first-line therapy mCRPC HRRms. Patients and Methods: BRCAAway is a biomarker preselected, randomized, phase 2 trial. BRCA1/2 and/or ATM alterations were randomized 1:1:1 to Arm1: abiraterone (1,000 mg)/prednisone (5 mg BID) (Abi/pred), Arm2: olaparib (300 (Ola), or Arm3: abiraterone/prednisone + (Abi/pred Ola). Single-agent arms could cross over at progression. Exploratory Arm4 other HRRms received alone. The primary endpoint was progression-free survival (PFS), secondary endpoints objective response, PSA safety. Results: Sixty-one 165 eligible had mutations: median age: 67 (IQR, 62–73) years. Mutations: BRCA1 n = 3, BRCA2 46, 11, multiple 1; 33 germline 28 somatic mutations. Median PFS [95% confidence interval (CI)]: Abi/pred, 8.6 months (m; 2.9, 17), Ola, 14 m (8.4, 20), Abi/pred 39 [22, not reached (NR)]. There no G4/5 adverse events; 8/19 on treatment crossed 8/21 vice versa. (95% CI) from crossover: Ola-after-Abi/pred, 8.3 (5.5, 15) Abi/pred-after-Ola, 7.2 (2.8, NR). randomization: 16 (7.8, 25) (11, Seventeen olaparib: CI): 5.5 (2, 11). Conclusions: In HRRm, Ola well tolerated longer either agent alone sequentially.

Language: Английский

Citations

15

Intensification Approaches and Treatment Sequencing in Metastatic Castration-resistant Prostate Cancer: A Systematic Review DOI
Edoardo Francini,

Neeraj Agarwal,

Elena Castro

et al.

European Urology, Journal Year: 2024, Volume and Issue: 87(1), P. 29 - 46

Published: Sept. 20, 2024

Language: Английский

Citations

6

Empowering PARP inhibition through rational combination: Mechanisms of PARP inhibitors and combinations with a focus on the treatment of metastatic castration-resistant prostate cancer DOI Creative Commons
Jinge Zhao, Bo Tang, Pengfei Shen

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2025, Volume and Issue: unknown, P. 104698 - 104698

Published: March 1, 2025

Language: Английский

Citations

0

Combination of PARP Inhibitors and Androgen Receptor Pathway Inhibitors in Metastatic Castration-Resistant Prostate Cancer DOI Creative Commons
Louise Kostos, Ben Tran, Arun Azad

et al.

Drugs, Journal Year: 2024, Volume and Issue: 84(9), P. 1093 - 1109

Published: July 26, 2024

Despite recent advances in the treatment of metastatic prostate cancer, progression to a castration-resistant state remains inevitable for most and prognosis is limited. Genetic testing homologous recombination repair pathway alterations recommended all patients with advanced cancer given that mutation present up 25% cases. Poly(ADP-ribose) polymerase (PARPis) are now approved use who have progressed on an androgen receptor inhibitor (ARPI) harbour germline or somatic mutation. Preclinical data support synergistic effect ARPI PARPi, various ARPI-PARPi combinations therefore been explored phase III clinical trials. heterogeneous findings, clear hierarchy benefit evident, harbouring BRCA deriving greatest magnitude benefit, followed by any The repair-proficient cohort less clear, questions remain about whether combination therapy should be offered without With ARPIs considered standard-of-care hormone-sensitive currently being earlier paradigm. purpose this review discuss rationale behind therapy, summarise results key trials, considerations future perspectives.

Language: Английский

Citations

4

DNA-Damaging Therapies in Patients With Prostate Cancer and Pathogenic Alterations in Homologous Recombination Repair Genes DOI
Laura Graham, Nicholas Henderson,

Olesia Kellezi

et al.

JCO Precision Oncology, Journal Year: 2024, Volume and Issue: 8

Published: Aug. 1, 2024

PURPOSE Outcomes data for DNA-damaging therapeutics men with prostate cancer (PC) and non- BRCA1/2 homologous recombination repair (HRR) mutations are limited. We evaluated outcomes by HRR alteration in PC treated poly(ADP-ribose)polymerase inhibitors (PARPi) and/or platinum chemotherapy. METHODS Retrospective from the PROMISE consortium were used. Clinical differences assessed between patients BRCA1/ 2 (cohort A) those without direct BRCA complex interaction B: ATM, CDK12, CHEK1, CHEK2, FANCL). also explored C: RAD51B/C/D, RAD54L2, BARD1, GEN1, PALB2, FANCA, BRIP1). RESULTS One hundred forty-six received PARPi A: 94, cohort 45, 7) 104 chemotherapy 48, 44, 10). PSA50 response rate to was higher A (61%) than B (5%), P < .001. Median clinical/radiographic progression-free survival (crPFS) significantly longer 15.9 versus 8.7 months, = .005. therapy (62%) (32%), .024, although crPFS not different. 40% 32%, respectively, C. In multivariable analysis, had improved overall compared but CONCLUSION Patients BRCA1/2-mutated interaction.

Language: Английский

Citations

4

A pan‐tumor review of the role of poly(adenosine diphosphate ribose) polymerase inhibitors DOI Open Access
Chadi Hage Chehade, Georges Gebrael, Nicolas Sayegh

et al.

CA A Cancer Journal for Clinicians, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Abstract Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors, such as olaparib, talazoparib, rucaparib, and niraparib, comprise a therapeutic class that targets PARP proteins involved in DNA repair. Cancer cells with homologous recombination repair defects, particularly BRCA alterations, display enhanced sensitivity to these agents because of synthetic lethality induced by inhibitors. These have significantly improved survival outcomes across various malignancies, initially gaining regulatory approval ovarian cancer subsequently breast, pancreatic, prostate cancers different indications. This review offers comprehensive clinical overview inhibitor approvals, emphasizing their efficacy based on landmark phase 3 trials.

Language: Английский

Citations

0

Präzisionsonkologie beim metastasierten kastrationsrefraktären Prostatakarzinom DOI

Lena Züllig

Urologie in der Praxis, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Citations

0

PARP Inhibitors and Prostate Cancer: The Struggle To Separate the Grain from the Chaff DOI

Elena Castro,

David Lorente, David Olmos

et al.

European Urology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0