Germline and Somatic Genomic Testing for Metastatic Prostate Cancer: ASCO Guideline

Journal of Clinical Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following guideline development process as outlined in Methodology Manual . follow Conflict Interest Policy Clinical Practice other guidance (“Guidance”) provided by is not a or definitive guide to treatment options. It intended voluntary use clinicians should be used conjunction independent professional judgment. Guidance may applicable all patients, interventions, diseases stages diseases. based on analysis literature, statement standard care. does endorse third-party drugs, devices, services, therapies assumes no responsibility any harm arising from related this information. See complete disclaimer Appendix 1 2 (online only) more PURPOSE To evaluate evidence germline somatic genomic testing patients metastatic prostate cancer recommendations. METHODS A systematic multidisciplinary panel patient representation was conducted. The PubMed database searched January 2018 May 2024. Articles were selected inclusion if they reported who received test and/or made comparisons between those tests, detection rates, prognostic information, implications. RESULTS total 1,713 papers identified search. After applying eligibility criteria, 14 remained: eight reviews six clinical trials. RECOMMENDATIONS Patients undergo both DNA sequencing using panel-based assays. These tests can poly(ADP-ribose) polymerase inhibitors, which have survival benefit castration-resistant cancer. In addition, screening implications additional cancers cascade family members. data supporting when perform repeat optimal tissue type (eg, primary tumor v biopsy versus circulating [ctDNA] testing) are limited, but recommends considering retesting whose results previously negative uninformative, consider either ctDNA significant change status occurs. Next-generation findings that associated only (and predictive) value outside trial. Additional information available at www.asco.org/genitourinary-cancer-guidelines

Language: Английский

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Heterogeneity of the Treatment Effect with PARP Inhibitors in Metastatic Castration-resistant Prostate Cancer: A Living Interactive Systematic Review and Meta-analysis

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

Published: Jan. 1, 2025

Language: Английский

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A pan‐tumor review of the role of poly(adenosine diphosphate ribose) polymerase inhibitors

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

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Empowering PARP inhibition through rational combination: Mechanisms of PARP inhibitors and combinations with a focus on the treatment of metastatic castration-resistant prostate cancer

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

Published: March 1, 2025

Language: Английский

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Talazoparib Plus Enzalutamide in Hrr-Deficient Metastatic Castration-Resistant Prostate Cancer: Final Overall Survival Results from the Phase 3 Talapro-2 Trial

Published: Jan. 1, 2025

Background Metastatic castration-resistant prostate cancer (mCRPC) remains incurable and is particularly aggressive in patients with homologous recombination repair (HRR) gene alterations. In TALAPRO-2, talazoparib plus enzalutamide significantly improved radiographic progression-free survival (rPFS) versus placebo mCRPC harbouring HRR At primary analysis, overall (OS) was immature.Methods Patients (N=399) asymptomatic/mildly symptomatic mCRPC, receiving ongoing androgen deprivation therapy, were prospectively assessed for tumour alterations randomised to once-daily (n=200) or (n=199) stratified by prior treatment castration-sensitive disease. We report the final prespecified OS analysis (a key alpha-protected secondary endpoint), updated rPFS, safety (ClinicalTrials.gov NCT03395197).Findings a median follow-up of 44.2 months (IQR 36·0–50·8), resulted statistically significant improvement (hazard ratio [HR] 0·62; 95% CI 0·48–0·81; 2-sided p=0·0005); 45·1 (95% 35·4–NR) 31·1 (27·3–35·4), respectively. subgroup BRCA1/2 (n=155), not reached 28·5 (HR 0·50; 0·32–0·78; p=0·0017); 4-year rates 53% 23%, without (n=244), 42·4 32·6 0·73; 0·52–1·02; p=0·066). Updated rPFS favoured 0·47; 0·36–0·61; p<0·0001); 30·7 12·3 months, No new signals identified; most common grade ≥3 adverse events anaemia (43%) neutropenia (20%).Interpretation Talazoparib showed clinically meaningful placebo, further establishing this combination as standard care HRR-deficient mCRPC. Funding Pfizer.KF reports honoraria (institution) participation advisory boards talks from Advanced Accelerator Applications/Novartis, Amgen, Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, Daiichi Sankyo, Janssen, MSD, Novartis, Pfizer, Sanofi; (personal) Arvinas, CureVac, MacroGenics, Orion. AAA Aculeus Therapeutics, Bristol Myers Squibb, Ipsen, Merck Serono, Sharp & Dohme, Noxopharm, Sanofi, Telix Pharmaceuticals, Tolmar; consulting fees Novartis; on Telix, data monitoring board OncoSec; research funding (institution unless stated otherwise) Aptevo Pharma (investigator), AstraZeneca Bionomics, Exelixis, Gilead Sciences, GlaxoSmithKline, Hinova Lilly, MedImmune, Serono (institutional), Synthorx; travel, accommodations, and/or expenses medical writing services support Pfizer; he Chair Urologic Oncology Group Clinical Society Australia, Translational Research Subcommittee Scientific Advisory Committee ANZUP Cancer Trials Group. NM Chugai Eisai, PRA Health Science, Roche, Seagen, Taiho, Takeda; Pfizer. JC has received personal serving consultant Johnson Johnson, MSD Novartis (AAA), participated speakers' bureau Johnson; her institution AB Aragon AROG AB, AVEO Bayer AG, Blueprint Medicines Corporation, BN Immunotherapeutics, Boehringer Ingelheim España, S.A., Squibb International Corporation (BMS), Cougar Biotechnology , Deciphera Pharmaceuticals LLC, F. Hoffmann-La Roche LTD, Genentech, SA, Incyte Janssen-Cilag NV, Karyopharm Laboratoires Leurquin Mediolanum SAS, Millennium Nanobiotix Farmacéutica, S.L.U., Puma Biotechnology, Sanofi-Aventis, SFJ LTD. II, Teva S.L.U.; travel/accommodations BMS, Roche. APF Roche; role stock options Brazilian Information Oncology; CAPES – CNPq, Foundation Medicine, UDG Dompé Farmaceutici, KGaA, PCCF RJJ Janssen. NDS AbbVie, Alessa Akido, Arquer, Asieris, Boston Scientific, CG Clarity Dendreon, Exact Imaging, FerGene, Ferring, FIZE Medical, GenesisCare, Guardant Health, ImmunityBio, Incyte, Invitae, Lantheus, Mdxhealth, Merck, Minomic, Myovant Myriad Genetics, Nymox, Pacific Edge Photocure, PlatformQ, Profound, Promaxo, Propella Protara, Sesen Bio, Speciality Networks, Tolmar, UroGen Vaxiion, Vessi; providing expert testimony Ferring; leadership other fiduciary another board, society, committee, advocacy group Photocure. CD Hengrui Laekna SZ payment lectures, presentations, speakers bureaus, manuscript writing, educational Amgen (personal institution), Eisai (personal), Janssen Pfizer institution); (institution), Ipsen (institution); Eisai; JO speaker BMS Norway, Janssen-Cilag, Pharma. NA (lifetime disclosures) reports: no COIs since April 15, 2021. Consultancy AVEO, Calithera, Clovis, Eli EMD Gilead, MEI Nektar, Pharmacyclics, Seattle Genetics. All authors have nothing declare.

Language: Английский

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Current androgen receptor antagonists under investigation for resistant prostate cancer: progress and challenges

Expert Review of Anticancer Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: March 16, 2025

Introduction Prostate cancer represents a significant oncological challenge, with its natural history predominantly driven by androgen receptor (AR) signaling. The pivotal role of this pathway underscores the rationale for targeting AR activity in therapeutic strategies. However, development resistance mechanisms has highlighted need advanced therapies to address complexity castration-resistant status.

Language: Английский

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State of the Art: Personalizing Treatment for Patients With Metastatic Castration-Resistant Prostate Cancer

American Society of Clinical Oncology Educational Book, Journal Year: 2025, Volume and Issue: 45(3)

Published: March 20, 2025

Until recently, the treatment of metastatic castration-resistant prostate cancer (mCRPC) relied exclusively on hormonal therapies and taxane chemotherapy. The advent modern molecular profiling methods applied in clinic, namely, next-generation sequencing advanced positron emission tomography (PET) imaging, has allowed for development biomarker-driven therapeutics including anti–PD-L1 therapy microsatellite instability-high or tumor mutation burden-high disease, poly(ADP-ribose) polymerase (PARP) inhibitors patients with DNA damage repair mutations, lutetium 177 vipivotide tetraxetan ( Lu-PSMA-617) prostate-specific membrane antigen (PSMA) PET-avid disease. While these targeted have improved outcomes, there is an opportunity to refine biomarkers optimize patient selection, understand resistance, develop novel combination strategies. In addition, studies laboratory patient-derived samples shown that a subset mCRPC tumors lose expression common markers such as PSMA because lineage plasticity non–androgen receptor (AR)-driven Non–AR-driven been associated aggressive behavior poor prognosis, some cases histologic transformation poorly differentiated neuroendocrine (NEPC). clinical management NEPC typically follows paradigm small cell lung increasingly relies genomic phenotypic characterization loss suppressors surface DLL3. Therefore, both subtyping are important consider can guide cancer.

Language: Английский

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Next-generation sequencing for guiding matched targeted therapies in people with relapsed or metastatic cancer

Cochrane library, Journal Year: 2025, Volume and Issue: 2025(3)

Published: March 24, 2025

Language: Английский

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Prognostic value of PARP1 and PARP2 copy number alterations in prostate cancer

Laboratory Investigation, Journal Year: 2025, Volume and Issue: unknown, P. 104171 - 104171

Published: April 1, 2025

Language: Английский

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Androgen Receptor Signaling Inhibition in Advanced Castration Resistance Prostate Cancer: What Is Expected for the Near Future?

Cancers, Journal Year: 2022, Volume and Issue: 14(24), P. 6071 - 6071

Published: Dec. 9, 2022

The androgen signaling pathway is the cornerstone in treatment of high risk or advanced prostate cancer patients. However, recent years, different mechanisms resistance have been defined this field, limiting efficacy currently approved antiandrogen drugs. Different therapeutic approaches are under research to assess role combination therapies against escape pathways development novel drugs try solve primary acquired dependent independent pathways. present review aims summarize current state inhibition algorithm patients with and those available In addition, conducted a comprehensive overview main future field receptor overcome these resistances potential new coming into setting.

Language: Английский

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