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Barcelona, Spain (UroToday.com) A proportion of patients with metastatic castration-resistant prostate cancer (mCRPC) have tumor cells harboring homologous recombination repair gene mutations that may confer sensitivity to poly ADP-ribose polymerase (PARP) inhibition1. The PROfound study is a Phase III, randomized, multicenter trial evaluating the efficacy and safety of the PARP inhibitor olaparib versus physician’s choice […]

Barcelona, Spain (UroToday.com) Rucaparib is a PARP inhibitor and has shown antitumor activity in patients with mCRPC and a deleterious DNA damage repair-deficient gene alteration. Initial results from the phase II TRITON2 study evaluating rucaparib in men who have progressed on an androgen receptor directed therapy and chemotherapy demonstrated confirmed radiographic and PSA responses in 44.0% […]

Barcelona, Spain (UroToday.com) Dr. Elena Castro discussed four important studies regarding PARP inhibitors presented at European Society for Medical Oncology (ESMO) 2019’s annual congress Prostate Cancer Session. These included: I. GALAHAD: (NCT02854436):A Phase II study assessing niraparib (300 mg daily) in patients with metastatic castration-resistant prostate cancer (mCRPC) and DNA repair defects (n=81) with disease progression […]

Barcelona, Spain (UroToday.com) In this session, Dr. Elena Castro discussed four prostate cancer abstracts: Dr. Castro began by reviewing that alterations in DNA damage repair (DDR) genes have been identified in approximately 20% of men with metastatic castration-resistant prostate cancer (mCRPC). The benefit of a synthetic lethality strategy with PARP inhibitors is being explored in […]

Barcelona, Spain (UroToday.com) Although once considered a homologous recombination DNA repair gene, cyclin-dependent kinase 12 (CDK12) is now thought to have a distinct role in maintaining genomic stability. In prostate cancer, inactivating CDK12 mutations, which are found in 6-7% of cases1, lead to gene fusion-induced neoantigens and possibly sensitivity to PD1 inhibitors. At the Prostate Cancer […]

Barcelona, Spain (UroToday.com) Effective therapies for patients with treatment-refractory metastatic castration-resistant prostate cancer (mCRPC) are an important unmet medical need. Niraparib is a highly selective poly ADP-ribose polymerase (PARP) inhibitor of PARP-1 and PARP-2 DNA-repair polymerases, proving effective for patients with mCRPC and DNA repair defects, initially presented at the 2019 ASCO meeting1. The Phase II GALAHAD study […]

Barcelona, Spain (UroToday.com) PD-L1 is overexpressed by dendritic cells of mCRPC patients progressing on androgen receptor antagonist therapy. Interestingly, anti-PD-1 agents lead to infrequent but durable responses. Combination of anti-PD-L1 and anti-CTLA-4 is a promising approach because of the non-redundant pathway blockade and synergy based on preclinical data, as well as emerging clinical data. In the […]

Barcelona, Spain (UroToday.com) Patients with metastatic castration-resistant prostate cancer (mCRPC) and disease progression after androgen receptor (AR) targeted therapy and taxane-based chemotherapy have a poor prognosis and few options for treatment. Preliminary evidence suggests that PARP inhibition is effective for patients with mCRPC and DNA repair defects (DRD). Niraparib is a highly selective PARP inhibitor […]

Barcelona, Spain (UroToday.com)  Although once considered a homologous recombination DNA repair gene, CDK12 is now thought to have a distinct role in maintaining genomic stability. In prostate cancer, inactivating CDK12 mutations lead to gene fusion-induced neoantigens, which may result in sensitivity to immunotherapeutic treatment strategy. The authors of this abstract conducted a retrospective, multicenter study […]