scholarly journals MP81-12 GALECTIN-3 IS INVOLVED IN THE TUMOR PROGRESSION AND DRUG RESISTANCE INDUCED BY TAXANE CHEMOTHERAPY AND POLY(ADENOSINE DIPHOSPHATE [ADP]-RIBOSE) POLYMERASE (PARP) INHIBITOR IN CASTRATION-RESISTANT PROSTATE CANCER

2019 ◽  
Vol 201 (Supplement 4) ◽  
Author(s):  
Tomoharu Fukumori* ◽  
Kei Daizumoto ◽  
Megumi Tsuda ◽  
Keisuke Ozaki ◽  
Yoshito Kusuhara ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Drug Resistance ◽  
Tumor Progression ◽  
Parp Inhibitor ◽  
Adenosine Diphosphate ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Galectin 3 ◽  
Taxane Chemotherapy

scholarly journals Prospective Multicenter Study of Circulating Tumor Cell AR-V7 and Taxane Versus Hormonal Treatment Outcomes in Metastatic Castration-Resistant Prostate Cancer

2020 ◽  
pp. 1285-1301
Author(s):  
Andrew J. Armstrong ◽  
Jun Luo ◽  
David M. Nanus ◽  
Paraskevi Giannakakou ◽  
Russell Z. Szmulewitz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Messenger Rna ◽  
Specific Antigen ◽  
Hormonal Treatment ◽  
Primary Objective ◽  
Castration Resistant Prostate Cancer ◽  
Protein Assay ◽  
Castration Resistant ◽  
Low Probability ◽  
Taxane Chemotherapy

PURPOSE Androgen receptor splice variant 7 (AR-V7) detection in circulating tumor cells (CTCs) is associated with a low probability of response and short progression-free (PFS) and overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide or abiraterone. However, it is unclear whether such men benefit from taxane chemotherapy. PATIENTS AND METHODS PROPHECY is a multicenter prospective blinded study of patients with poor-risk mCRPC starting abiraterone or enzalutamide and observed through subsequent progression and taxane chemotherapy. We assessed AR-V7 status using the Johns Hopkins modified AdnaTest CTC AR-V7 messenger RNA assay and the Epic Sciences CTC nuclear-localized AR-V7 protein assay before treatment. The primary objective was to validate the independent prognostic value of CTC AR-V7 status based on radiographic/clinical PFS. OS, confirmed prostate-specific antigen (PSA), and objective radiologic responses were secondary end points. RESULTS We enrolled 118 men with mCRPC treated with abiraterone or enzalutamide, 51 of whom received subsequent docetaxel or cabazitaxel. Pretreatment CTC AR-V7 status by the Johns Hopkins and Epic Sciences assays was independently associated with worse PFS (hazard ratio [HR], 1.7; 95% CI, 1.0 to 2.9 and HR, 2.1; 95% CI, 1.0 to 4.4, respectively) and OS (HR, 3.3; 95% CI, 1.7 to 6.3 and HR, 3.0; 95% CI, 1.4 to 6.3, respectively) and a low probability of confirmed PSA responses, ranging from 0% to 11%, during treatment with abiraterone or enzalutamide. At progression, subsequent CTC AR-V7 detection was not associated with an inferior PSA or radiographic response or worse PFS or OS with subsequent taxane chemotherapy after adjusting for CellSearch CTC enumeration and clinical prognostic factors. CONCLUSION Detection of AR-V7 in CTCs by two different blood-based assays is independently associated with shorter PFS and OS with abiraterone or enzalutamide, but such men with AR-V7–positive disease still experience clinical benefits from taxane chemotherapy.

A phase Ib/II study of niraparib combination therapies for the treatment of metastatic castration-resistant prostate cancer (NCT03431350).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS5087-TPS5087 ◽  
Author(s):  
Sumit Kumar Subudhi ◽  
Ana Aparicio ◽  
Amado J. Zurita ◽  
Bernard Doger ◽  
William Kevin Kelly ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Parp Inhibitor ◽  
Rapid Identification ◽  
Abiraterone Acetate ◽  
Parp Inhibition ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Castration Resistant ◽  
Abstract Submission

TPS5087 Background: Assessing multiple therapies in a single clinical trial can facilitate the rapid identification of new agents for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). Niraparib (Nirap) is a highly selective PARP inhibitor, with potent activity against PARP-1 and PARP-2 deoxyribonucleic acid (DNA)-repair polymerases. PARP inhibition may be especially lethal in tumor cells with genetic DNA damage response deficits (DRD). Based on promising preclinical and clinical data, this study is designed as a master protocol with nirap as a backbone therapy. Combination 1 assesses the safety and efficacy of nirap plus JNJ-63723283 (JNJ-283), an anti-PD-1 monoclonal antibody. Combination 2 assesses nirap plus abiraterone acetate and prednisone (AA-P). Methods: This multicenter, global, open-label study is currently open at 18 sites in 5 countries of the planned XX sites, and is enrolling patients with mCRPC who have progressed on ≥1 androgen-receptor targeted therapy for mCRPC. Enrollment at time of abstract submission was 25 for combination 1. When combined with AA-P, the RP2D has been determined to be nirap 200 mg. The recommended phase-2 dose (RP2D) of nirap plus JNJ-283 was determined in Part 1 based on the incidence of specified adverse events and PK data to be 480 mg every 4 weeks. For Part 2 of the study, patients are assigned to receive oral niraparib daily plus JNJ-283 infusions once every four weeks until disease progression, unacceptable toxicity, death, study termination. Part 2 is described in the table. Clinical trial information: NCT03431350. [Table: see text]

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