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https://www.readbyqxmd.com/read/28633425/androgen-receptor-mutations-in-patients-with-castration-resistant-prostate-cancer-treated-with-apalutamide
#1
D E Rathkopf, M R Smith, C J Ryan, W R Berry, N D Shore, G Liu, C S Higano, J J Alumkal, R Hauke, R F Tutrone, M Saleh, E Chow Maneval, S Thomas, D S Ricci, M K Yu, C J de Boer, A Trinh, T Kheoh, R Bandekar, H I Scher, E S Antonarakis
Background: : Mutations in the androgen receptor (AR) ligand-binding domain (LBD), such as F877L and T878A, have been associated with resistance to next-generation AR-directed therapies. ARN-509-001 was a phase I/II study that evaluated apalutamide activity in castration-resistant prostate cancer (CRPC). Here we evaluated the type and frequency of 11 relevant AR-LBD mutations in apalutamide-treated CRPC patients. Patients and methods: : Blood samples from men with non-metastatic CRPC (nmCRPC) and metastatic CRPC (mCRPC) pre- or post abiraterone acetate and prednisone (AAP) treatment (≥6 months' exposure) were evaluated at baseline and disease progression in trial ARN-509-001...
June 15, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28628393/early-national-dissemination-of-abiraterone-and-enzalutamide-for-advanced-prostate-cancer-in-medicare-part-d
#2
Megan E V Caram, Tudor Borza, Hye-Sung Min, Jennifer J Griggs, David C Miller, Brent K Hollenbeck, Bhramar Mukherjee, Ted A Skolarus
INTRODUCTION: Abiraterone and enzalutamide were approved by the Food and Drug Administration in 2011 and 2012 to treat men with metastatic castration-resistant prostate cancer (mCRPC). Most men with mCRPC are > 65 years of age and thus eligible for Medicare Part D. We conducted a study to better understand the early dissemination of these drugs across the United States using national Medicare Part D data. METHODS: We evaluated the number of prescriptions for abiraterone and enzalutamide by provider specialty and hospital referral region (HRR) using Medicare Part D and Dartmouth Atlas data...
June 19, 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28624848/-177-lu-psma-617-radioligand-therapy-and-outcome-in-patients-with-metastasized-castration-resistant-prostate-cancer
#3
Axel Bräuer, Lena Sophie Grubert, Wolfgang Roll, Andres Jan Schrader, Michael Schäfers, Martin Bögemann, Kambiz Rahbar
PURPOSE: Radioligand therapies targeting prostate-specific membrane antigen (PSMA) have been established for the treatment of metastasized castration-resistant prostate cancer (mCRPC) in the last decade and show promising response rates and a favourable toxicity profile. The aim of this study was to evaluate the overall survival (OS) and to identify parameters predicting outcome in mCRPC patients treated with (177)Lu-PSMA-617. METHODS: Between December 2014 and January 2017, 59 consecutive patients (median age 72 years; interquartile range, (IQR, 66-76 years) with mCRPC, who had been treated with at least one next-generation antihormonal drug as well as chemotherapy, were included in this study...
June 17, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28623073/commentary-on-biallelic-inactivation-of-brca2-in-platinum-sensitive-metastatic-castration-resistant-prostate-cancer-cheng-hh-pritchard-cc-boyd-t-nelson-ps-montgomery-b-eur-urol-jun-2016-69-6-992-5
#4
Stephen Freedland, William Aronson
Understanding the molecular underpinnings of sensitivity to specific therapies will advance the goal of precision medicine in prostate cancer (PCa). We identified 3 patients with metastatic castration-resistant PCa (mCRPC) who achieved an exceptional response to platinum chemotherapy (not first-line treatment for PCa), despite disease progression on prior standard therapies. Using targeted next-generation sequencing on the primary and metastatic tumors, we found that all 3 patients had biallelic inactivation of BRCA2, a tumor suppressor gene critical for homologous DNA repair...
June 13, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28623072/commentary-on-integrative-clinical-genomics-of-advanced-prostate-cancer-robinson-d-van-allen-em-wu-ym-schultz-n-lonigro-rj-mosquera-jm-montgomery-b-taplin-me-pritchard-cc-attard-g-beltran-h-abida-w-bradley-rk-vinson-j-cao-x-vats-p-kunju-lp-hussain-m-feng-fy
#5
Stephen J Freedland, William J Aronson
Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%-60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF...
June 13, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28621316/combination-of-p53-dc-vaccine-and-rad-p53-gene-therapy-induced-ctls-cytotoxic-against-p53-deleted-human-prostate-cancer-cells-in-vitro
#6
H Saito, K Kitagawa, T Yoneda, Y Fukui, M Fujsawa, D Bautista, T Shirakawa
Recently, the US FDA approved sipuleucel-T, which is composed of autologous DCs stimulated with a recombinant fusion protein of prostatic acid phosphatase (PAP) and granulocyte-macrophage colony-stimulating factor (GM-CSF), as the first immunotherapeutic agent for metastatic castration resistant prostate cancer (mCRPC). However, sipuleucel-T demonstrated only modest efficacy in mCPRC patients. Researchers are now investigating the potential of p53 protein as a tumor-associated antigen (TAA) loaded in DC-based cancer vaccine...
June 16, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28614883/-monitoring-of-treatment-for-metastatic-castration-resistant-prostate-cancer
#7
Stefan Hinz
Treatments currently available for metastatic castration-resistant prostate cancer (mCRPC) include abiraterone acetate, enzalutamide, docetaxel, cabazitaxel, and radium-223. However, the optimal sequence of these agents is still unclear, and markers to predict treatment response and facilitate patient selection remain an unmet need. In terms of overall survival, it is crucial that patients receive all treatment options currently available. This requires early detection of progression as an indication for a treatment switch...
May 2017: Aktuelle Urologie
https://www.readbyqxmd.com/read/28614882/-review-on-quality-of-life-in-crpc-patients
#8
Kurt Miller
Health-related quality of life (HRQoL) deteriorates rapidly in patients with advanced-stage cancer, with patients seriously disturbed by fatigue, sleep disorders, bone pain, constipation and other disease related symptoms. As treatment and prognosis continues to improve, reducing symptoms and improving quality of life with minimum of toxicities have become important therapeutic goals. The effectiveness of abiraterone acetate and enzalutamide in both prolonging life and improving quality of life in asymptomatic or mildly symptomatic patients with metastatic castrations-resistant prostate cancer (mCRPC) has been clinically proven...
May 2017: Aktuelle Urologie
https://www.readbyqxmd.com/read/28614217/psa-declines-and-survival-in-patients-with-metastatic-castration-resistant-prostate-cancer-treated-with-enzalutamide-a-retrospective-case-report-study
#9
Davide Bosso, Martina Pagliuca, Guru Sonpavde, Gregory Pond, Giuseppe Lucarelli, Sabrina Rossetti, Gaetano Facchini, Sarah Scagliarini, Giacomo Cartenì, Bruno Daniele, Franco Morelli, Matteo Ferro, Livio Puglia, Michela Izzo, Vittorino Montanaro, Teresa Bellelli, Francesca Vitrone, Sabino De Placido, Carlo Buonerba, Giuseppe Di Lorenzo
RATIONALE: PSA responses have been associated with a survival benefit in patients treated with enzalutamide in retrospective analyses. PATIENT CONCERNS: However the prognostic value of PSA declines in highly pretreated patients receiving enzalutamide remains to be defined. DIAGNOSES AND INTERVENTATIONS: Medical records of patients with documented mCRPC treated with enzalutamide between September 2011 and August 2016 were reviewed at multiple participating centers and assessed for overall survival (OS), PSA variations, and other variables of interest...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28608115/phase-i-trial-of-antigen-targeted-autologous-dendritic-cell-based-vaccine-with-in-vivo-activation-of-inducible-cd40-for-advanced-prostate-cancer
#10
Guru Sonpavde, John D McMannis, Yu Bai, Mamatha R Seethammagari, Joan M C Bull, Victoria Hawkins, Theresa K Dancsak, Natasha Lapteva, Jonathan M Levitt, Annemarie Moseley, David M Spencer, Kevin M Slawin
This phase I trial reports the safety and activity of BPX101, a second-generation antigen-targeted autologous antigen presenting cell (APC) vaccine in men with metastatic castration-resistant prostate cancer (mCRPC). To manufacture BPX101, APCs collected in a single leukapheresis were transduced with adenoviral vector Ad5f35 encoding inducible human (ih)-CD40, followed by incubation with protein PA001, which contains the extracellular domain of human prostate-specific membrane antigen. The ih-CD40 represents a modified chimeric version of the dendritic cell (DC) co-stimulatory molecule, CD40, which responds to a bioinert membrane-permeable activating dimerizer drug, rimiducid (AP1903), permitting temporally controlled, lymphoid-localized, DC-specific activation...
June 12, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28604629/androgen-receptor-dependent-and-independent-mechanisms-involved-in-prostate-cancer-therapy-resistance
#11
REVIEW
Daniel J Crona, Young E Whang
Despite the initial efficacy of androgen deprivation in prostate cancer, virtually all patients progress to castration-resistant prostate cancer (CRPC). Androgen receptor (AR) signaling is critically required for CRPC. A new generation of medications targeting AR, such as abiraterone and enzalutamide, has improved survival of metastatic CRPC (mCRPC) patients. However, a significant proportion of patients presents with primary resistance to these agents, and in the remainder, secondary resistance will invariably develop, which makes mCRPC the lethal form of the disease...
June 12, 2017: Cancers
https://www.readbyqxmd.com/read/28604117/efficacy-and-safety-of-post-docetaxel-therapies-in-metastatic-castrate-resistant-prostate-cancer-a-systematic-review-of-the-literature
#12
Nicholas Summers, Jacqueline Vanderpuye-Orgle, Marcia Reinhart, Meghan Gallagher, Oliver Sartor
OBJECTIVE: Prostate cancer is a highly prevalent form of cancer in older men and is one of the leading causes of death from cancer in men across the globe. Many therapeutic agents have been approved for patients with metastatic castrate-resistant prostate cancer (mCRPC), particularly as a post-docetaxel treatment strategy. The objective of this systematic literature review was to assess published efficacy and safety data for select mCRPC therapies - such as abiraterone, cabazitaxel, and enzalutamide - in the post-docetaxel setting...
June 12, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28590268/ar-v7-liquid-biopsy-for-treatment-stratification-in-prostate-cancer-how-close-are-we
#13
Claire Fletcher
PURPOSE OF REVIEW: Recent clinical introduction of the novel antiandrogen, Enzalutamide (Enza), CYP17 inhibitor, Abiraterone (Abi), and the second-generation chemotherapeutic, Cabazitaxel, has increased survival of patients with advanced, metastatic castration-resistant prostate cancer (mCRPC). However, de novo and acquired resistance rates are high. A liquid biopsy that can rapidly, sensitively and robustly identify which patients will respond to treatment in a minimally invasive manner is urgently required to permit switch to a potentially more efficacious drug regimen, thus increasing survival whilst avoiding debilitating side effects associated with unnecessary treatment...
June 5, 2017: Current Opinion in Urology
https://www.readbyqxmd.com/read/28589907/improving-circulating-tumor-cells-enumeration-and-characterization-to-predict-outcome-in-first-line-chemotherapy-mcrpc-patients
#14
Luis León-Mateos, Helena Casas, Alicia Abalo, María Vieito, Manuel Abreu, Urbano Anido, Antonio Gómez-Tato, Rafael López, Miguel Abal, Laura Muinelo-Romay
INTRODUCTION: There is a critical need of new surrogate markers for improving the therapeutic selection and monitoring of metastatic prostate cancer patients. Nowadays clinical management of these patients is been driven by biochemical and clinical parameters without enough accuracy to allow a real personalized medicine. The present study was conducted to go insight the molecular profile of circulating tumor cells (CTCs) isolated from advanced metastatic castration-resistant prostate cancer (mCRPC) with the aim of identifying prognostic marker with potential utility for therapy selection and monitoring...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28579151/validation-of-the-association-of-recist-changes-with-survival-in-men-with-metastatic-castration-resistant-prostate-cancer-treated-on-swog-study-s0421
#15
Guru Sonpavde, Gregory R Pond, Melissa Plets, Catherine M Tangen, Maha H A Hussain, Primo N Lara, Amir Goldkorn, Mark G Garzotto, Philip C Mack, Celestia S Higano, Nicholas J Vogelzang, Ian M Thompson, Przemyslaw W Twardowski, Peter J Van Veldhuizen, Neeraj Agarwal, Michael A Carducci, J Paul Monk, David I Quinn
BACKGROUND: Phase 2 trials evaluating new agents for metastatic castration-resistant prostate cancer (mCRPC) have relied on bone scan and prostate-specific antigen changes to assess activity. Given the increasing detection of measurable disease, Response Evaluation Criteria in Solid Tumors (RECIST) changes warrant consideration to evaluate activity. We validated the association of RECIST 1.0 changes with survival in men with mCRPC receiving docetaxel. PATIENTS AND METHODS: Data for men with measurable disease from the Southwest Oncology Group (SWOG) S0421, a phase 3 trial in men with mCRPC receiving docetaxel and prednisone plus placebo or atrasentan, were used...
May 10, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28549709/ct-guided-bone-biopsies-in-metastatic-castration-resistant-prostate-cancer-factors-predictive-of-maximum-tumor-yield
#16
Michael G Holmes, Erik Foss, Gabby Joseph, Adam Foye, Brooke Beckett, Daria Motamedi, Jack Youngren, George V Thomas, Jiaoti Huang, Rahul Aggarwal, Joshi J Alumkal, Tomasz M Beer, Eric J Small, Thomas M Link
PURPOSE: To evaluate the success rate of CT-guided bone biopsies in metastatic castration-resistant prostate cancer (mCRPC) and to investigate associated technical, imaging, and clinical parameters affecting diagnostic yields. MATERIALS AND METHODS: Eighty CT-guided bone biopsy specimens were obtained from 72 men (median age, 68 y; range, 49-89 y) enrolled in a multicenter trial to identify mechanisms of resistance in mCRPC. Successful biopsy was determined by histologic confirmation of tumor cells and successful isolation of RNA for molecular analysis...
May 24, 2017: Journal of Vascular and Interventional Radiology: JVIR
https://www.readbyqxmd.com/read/28548924/comparing-the-clinical-efficacy-of-abiraterone-acetate-enzalutamide-and-orteronel-in-patients-with-metastatic-castration-resistant-prostate-cancer-by-performing-a-network-meta-analysis-of-eight-randomized-controlled-trials
#17
Minyong Kang, Chang Wook Jeong, Cheol Kwak, Ja Hyeon Ku, Hyeon Hoe Kim
Various novel androgen receptor (AR) targeting drugs have been developed recently and have shown beneficial effects on survival in patients with metastatic castration-resistant prostate cancer (mCRPC). However, no consensus has been reached regarding which of these agents provides the most favorable oncological outcomes. Here, we aimed to compare the efficacy of novel AR-targeted agents by performing a network meta-analysis of randomized controlled trials (RCTs). We included eight RCTs for men with mCRPC treated with one of the AR targeting agents: abiraterone acetate, enzalutamide, or orteronel...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28545997/factors-associated-with-survival-following-radium-223-treatment-for-metastatic-castration-resistant-prostate-cancer
#18
William W Wong, Eric M Anderson, Homan Mohammadi, Thomas B Daniels, Steve E Schild, Sameer R Keole, C Richard Choo, Katherine S Tzou, Alan H Bryce, Thai H Ho, Fernando J Quevedo, Sujay A Vora
BACKGROUND: Radium-223 ((223)Ra) improves survival in patients with metastatic castration-resistant prostate cancer (mCRPC). This retrospective analysis was performed to better understand its efficacy in routine clinical practice and identify factors associated with survival. MATERIALS AND METHODS: Sixty-four patients with mCRPC who received (223)Ra between 2013 and 2015 were the basis of this retrospective study. Clinical outcomes and patient characteristics were obtained...
April 26, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28545929/a-simple-hplc-uv-method-for-quantification-of-enzalutamide-and-its-active-metabolite-n-desmethyl-enzalutamide-in-patients-with-metastatic-castration-resistant-prostate-cancer
#19
Alicja Puszkiel, Alain Plé, Olivier Huillard, Gaëlle Noé, Constance Thibault, Stéphane Oudard, François Goldwasser, Michel Vidal, Jérome Alexandre, Benoit Blanchet
Enzalutamide is currently approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). To date, a single liquid chromatographic-tandem mass spectroscopy method is available to measure plasma enzalutamide concentrations in mCRPC patients. In this work, an accurate and sensitive HPLC-UV method has been developed for the simultaneous determination of enzalutamide and its active metabolite, N-desmethyl enzalutamide in plasma from mCRPC patients. Before precipitation of proteins with acetonitrile, samples were spiked with nilutamide (internal standard)...
April 5, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28532278/tackling-non-metastatic-castration-resistant-prostate-cancer-special-considerations-in-treatment
#20
Archana Anantharaman, Eric J Small
Prostate cancer (PCa) is currently the second most common cancer affecting men worldwide. Metastatic castration-resistant prostate cancer (mCRPC) is the incurable form of PCa, carrying the poorest prognosis, and can develop from non-metastatic CRPC (M0 CRPC). CRPC is defined as progression of the disease with castrate level testosterone levels, achieved with primary androgen deprivation therapy (ADT). M0 CRPC is a highly heterogeneous disease process lacking clear standard of care therapies. Areas covered: In this review, a broad literature search was undertaken to explore data available for therapeutic options and guidelines in the management of M0 CRPC...
May 31, 2017: Expert Review of Anticancer Therapy
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