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STATE-OF-THE-INDUSTRY VIDEOS BY LEADING UROLOGY EXPERTS |
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Integrating PARP inhibitors into the Standard of Care for Prostate Cancer
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Joaquin Mateo, MD, PhD
Joaquin Mateo, Principal Investigator, and Translational Scientist at the Vall d'Hebron hospital in Barcelona joins Charles Ryan to discuss how PARP inhibitors are being integrated into the standard of care for prostate cancer, pivotal studies that are reporting and ongoing with PARP inhibitors, and important aspect of those studies that clinicians should integrate into his or her clinical daily life.
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Monoallelic versus Biallelic BRCA2 Alterations, PARP Inhibitors in Prostate Cancer
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Colin Pritchard, MD, PhD
Colin Pritchard joins Charles Ryan at the 26th Annual Prostate Cancer Foundation Scientific Retreat (PCF 2019) where they discuss PARP inhibitor data that came out of the 2019 ESMO meeting including the PROfound study data, rucaparib in TRITON2, and niraparib in the GALAHAD study and focusing on monoallelic versus biallelic BRCA2 alterations.
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Management of Castration-Resistant Prostate Cancer
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Cora Sternberg MD, FACP
Cora Sternberg joins Alicia Morgans and shares highlights from the Management of castration-resistant prostate cancer session at the 2019 Advanced Prostate Cancer Consensus Conference and key takeaways from the session when thinking about managing these patients with this disease.
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PARP Inhibition for Metastatic Castration-Resistant Prostate Cancer Presentation |
Kim Chi, MD, FRCPC |
Kim Chi presented an update on the utilization of PARP inhibitors for treatment of CRPC. Leading his presentation with the most recent positive phase III results from Lynparza® (olaparib), the only PARP inhibitor with positive phase III results in four different cancer types. |
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PROfound Study - PARP-inhibitor Olaparib in Advanced Prostate Cancer Patients with Specific Tumor Mutations
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Maha Hussain, MD, FACP, FASCO
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Maha Hussain joins Alicia Morgans sharing an overview of the PROfound study design, it's intent, and specifications on how it was designed to arrive at the answer it was seeking. Investigators wanted to look at the spectrum of potential DNA repair defective pathways and at the same time aimed to avoid diluting the results which led to looking at two separate cohorts.
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RECENT DATA FROM CONFERENCES WORLDWIDE |
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PARP Inhibitors for Prostate Cancer
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Joaquin Mateo, MD, PhD
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Joaquin Mateo provided an overview of PARP inhibitors in prostate cancer. Metastatic prostate cancer remains a lethal disease, however, abiraterone, enzalutamide, and radium-223 have prolonged survival. Currently, the one-size-fits-all approach remains the standard of care in metastatic castration-resistant prostate cancer (mCRPC). As we learn more about mCRPC, Dr. Mateo notes that we identify potential additional targets for tailored treatment.
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CDK12-Altered Prostate Cancer: Clinical Features and Therapeutic Outcomes to Standard Systemic Therapies, PARP and PD1 Inhibitors
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Emmanuel Antonarakis, MB, BCh
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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 cases, lead to gene fusion-induced neoantigens and possibly sensitivity to PD1 inhibitors. Dr. Antonarakis and colleagues presented results of their study assessing outcomes of patients with CDK12 loss-of-function mutations.
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GALAHAD - A Phase 2 Study of Niraparib in Patients with mCRPC and Biallelic DNA-Repair Gene Defects, A Pre-Specified Interim Analysis
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Matthew Smith, MD, PhD
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GALAHAD is an ongoing open-label phase 2 study assessing niraparib (300 mg daily) in patients with mCRPC and DNA repair defects (DRD) with disease progression on androgen receptor targeted therapy and taxane-based chemotherapy. DRD status was evaluated by a plasma or tissue-based test and defined as having biallelic alterations in BRCA1/2 (BRCA), ATM, FANCA, PALB2, CHEK2, BRIP1, or HDAC2. The primary endpoint was objective response rate by RECIST 1.1 with no evidence of bone progression as per the prostate cancer working group 3 (PCWG3) criteria.
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Preliminary Results from the TRITON2 Study of Rucaparib in Patients with DNA Damage Repair-deficient mCRPC: Updated Analyses
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Wassim Abida, MD, PhD
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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% and 51.1% of patients with a deleterious BRCA1/2 alteration.
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Poly ADP Ribose Polymerase (PARP) Inhibitors for Prostate Cancer
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Joaquin Mateo, MD, PhD
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Joaquin Mateo presented an overview of the use of poly ADP ribose polymerase (PARP) inhibitors in the treatment of metastatic prostate cancer, from their biological rationale, to the preliminary data suggesting their efficacy, and finally to a review of the recent PROfound randomized phase III trial.
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TOPARP-B: A Phase II Randomized Trial of the Poly(ADP)-Ribose Polymerase Inhibitor Olaparib for Metastatic Castration Resistant Prostate Cancers with DNA Damage Repair Alterations - Medical Oncologist Perspective
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Joaquin Mateo, MD, PhD
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Joaquin Mateo presented on the findings of TOPARP-B, the second stage of the trial where patients are pre-selected based on the detection of DNA repair defects. This abstract reports data on 98 patients with putatively pathogenic DNA damage repair (DDR) alterations who were randomized to either 300 mg or 400 mg of olaparib. Of note in TOPARP B, a second cohort was added at 300 mg given that this dose had been approved for other disease types.
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Invited Discussant: (LBA50, 845PD, 846PD and 847PD) Phase 2 Study GALAHAD, CDK12-altered Prostate Cancer, Preliminary results from the TRITON2 study, and HRRm in Tumor Tissue from men with mCRPC Screened for the PROfound Study
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Elena Castro, MD, PhD
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Elena Castro discusses four prostate cancer abstracts. She 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 several clinical trials.
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