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Joaquim bellmunt

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https://www.readbyqxmd.com/read/29765151/apatorsen-plus-docetaxel-versus-docetaxel-alone-in-platinum-resistant-metastatic-urothelial-carcinoma-borealis-2
#1
Jonathan E Rosenberg, Noah M Hahn, Meredith M Regan, Lillian Werner, Ajjai Alva, Saby George, Joel Picus, Robert Alter, Arjun Balar, Jean Hoffman-Censits, Petros Grivas, Richard Lauer, Elizabeth A Guancial, Christopher Hoimes, Guru Sonpavde, Constantine Albany, Mark N Stein, Tim Breen, Cindy Jacobs, Kirsten Anderson, Joaquim Bellmunt, Aly-Khan A Lalani, Sumanta Pal, Toni K Choueiri
BACKGROUND: A randomised study to assess the addition of apatorsen, an antisense oligonucleotide that inhibits Hsp27 expression, to docetaxel in patients with metastatic urothelial carcinoma (mUC) relapsed after prior platinum-based chemotherapy. METHODS: Multicentre, phase II study with 1:1 randomisation to apatorsen (three loading doses at 600 mg intravenous followed by weekly doses) plus docetaxel (75 mg/m2 intravenous every 21 days) (A/D) or docetaxel alone...
May 16, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29755651/the-clinical-impact-of-using-complex-molecular-profiling-strategies-in-routine-oncology-practice
#2
Jean-François Laes, Philippe Aftimos, Philippe Barthelemy, Joaquim Bellmunt, Guy Berchem, Carlos Camps, Ramón de Las Peñas, Ana Finzel, Jesús García-Foncillas, Petteri Hervonen, Ibrahim Wahid, Timo Joensuu, Louis Kathan, Anthony Kong, James Mackay, Christos Mikropoulos, Kefah Mokbel, Jean-Loup Mouysset, Sergey Odarchenko, Timothy J Perren, Rika Pienaar, Carlos Regonesi, Shadi Salem Alkhayyat, Abdul Rahman El Kinge, Omalkhair Abulkhair, Khaled Morsi Galal, Hady Ghanem, Fadi El Karak, Angel Garcia, Gregori Ghitti, Helen Sadik
Molecular profiling and functional assessment of signalling pathways of advanced solid tumours are becoming increasingly available. However, their clinical utility in guiding patients' treatment remains unknown. Here, we assessed whether molecular profiling helps physicians in therapeutic decision making by analysing the molecular profiles of 1057 advanced cancer patient samples after failing at least one standard of care treatment using a combination of next-generation sequencing (NGS), immunohistochemistry (IHC) and other specific tests...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29706503/nomogram-to-assess-the-survival-benefit-of-new-salvage-agents-for-metastatic-urothelial-carcinoma-in-the-era-of-immunotherapy
#3
Guru Sonpavde, Gregory Russell Pond, Jonathan E Rosenberg, Toni K Choueiri, Joaquim Bellmunt, Ashley Marie Regazzi, Stephanie A Mullane, Andrea Necchi, Daniele Raggi, Jae-Lyun Lee, Soonil Lee, Joe Simpson, Christina Louise Derleth, Shih-Wen Lin, Dean F Bajorin
INTRODUCTION: Optimal end points in phase 2 trials evaluating salvage therapy for metastatic urothelial carcinoma are necessary to identify promising drugs, particularly immunotherapeutics, where response and progression-free survival may be unreliable. We developed a nomogram using data from phase 2 trials of historical agents to estimate the 12-month overall survival (OS) for patients to which observed survival of nonrandomized data sets receiving immunotherapies could be compared. PATIENTS AND METHODS: Survival and data for major prognostic factors were obtained from phase 2 trials: hemoglobin, performance status, liver metastasis, treatment-free interval, and albumin...
April 6, 2018: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29590008/health-related-quality-of-life-analysis-from-keynote-045-a-phase-iii-study-of-pembrolizumab-versus-chemotherapy-for-previously-treated-advanced-urothelial-cancer
#4
David J Vaughn, Joaquim Bellmunt, Yves Fradet, Jae Lyun Lee, Lawrence Fong, Nicholas J Vogelzang, Miguel A Climent, Daniel P Petrylak, Toni K Choueiri, Andrea Necchi, Winald Gerritsen, Howard Gurney, David I Quinn, Stephane Culine, Cora N Sternberg, Yabing Mai, Haojie Li, Rodolfo F Perini, Dean F Bajorin, Ronald de Wit
Purpose In the phase III KEYNOTE-045 study ( ClinicalTrials.gov identifier: NCT02256436), pembrolizumab significantly prolonged overall survival compared with investigator's choice of chemotherapy in patients with previously treated advanced urothelial cancer. Here, we report the results of health-related quality-of-life (HRQoL) analyses from the KEYNOTE-045 trial. Patients and Methods Patients were randomly assigned 1:1 to pembrolizumab 200 mg or investigator's choice of docetaxel 75 mg/m2 , paclitaxel 175 mg/m2 , or vinflunine 320 mg/m2 administered intravenously every 3 weeks...
March 28, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29550200/results-of-the-flac-european-database-of-metastatic-castration-resistant-prostate-cancer-patients-treated-with-docetaxel-cabazitaxel-and-androgen-receptor-targeted-agents
#5
Antoine Angelergues, Eleni Efstathiou, Revekka Gyftaki, Piotr Jan Wysocki, Nuria Lainez, Iria Gonzalez, Daniel E Castellano, Mustafa Ozguroglu, Iciar Garcia Carbonero, Aude Flechon, Pablo Borrega, Aline Guillot, Begona Campos Balea, Sylvestre Le Moulec, Emilio Esteban, Javier Munarriz, Gustavo Rubio, Alison J Birtle, Nicolas Delanoy, Joaquim Bellmunt, Stéphane Oudard
BACKGROUND: Several agents have demonstrated an overall survival (OS) benefit in patients with metastatic castration-resistant prostate cancer (mCRPC); however, the optimal sequencing of these therapies is unknown as a result of a lack of prospective randomized controlled trials. This retrospective study aimed to identify clinical factors influencing outcomes and to determine optimal treatment sequencing in patients with mCRPC treated with cabazitaxel (CABA) and/or androgen receptor-targeted agents (ART) after androgen-deprivation therapy (ADT) and docetaxel (DOC)...
February 23, 2018: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29540084/avelumab-for-the-treatment-of-urothelial-cancer
#6
Alejo Rodriguez-Vida, Joaquim Bellmunt
Metastatic urothelial carcinoma (UC) remains an aggressive disease associated with limited treatment options and a reduced survival. In spite of this, the first-line treatment based on platinum-based combinations has remained virtually unchanged for the last 20-30 years. Similarly, before the advent of the immune checkpoint inhibitors, there were no FDA-approved drugs for second-line therapy. In the last few years, impressive signs of anti-tumor activity have been reported with several immunotherapy agents targeting the programmed cell death-1 (PD-1) pathway...
May 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29478735/atezolizumab-in-platinum-treated-locally-advanced-or-metastatic-urothelial-carcinoma-clinical-experience-from-an-expanded-access-study-in-the-united-states
#7
Sumanta Kumar Pal, Jean Hoffman-Censits, Hanzhe Zheng, Constanze Kaiser, Darren Tayama, Joaquim Bellmunt
BACKGROUND: Atezolizumab (anti-programmed death-ligand 1) was approved in the USA, Europe, and elsewhere for treatment-naive and platinum-treated locally advanced/metastatic urothelial carcinoma (mUC). OBJECTIVE: To report efficacy and safety from an atezolizumab expanded access study. DESIGN, SETTING, AND PARTICIPANTS: This single-arm, open-label study enrolled 218 patients at 36 US sites. Key eligibility criteria included progression during/following ≥1 platinum-based chemotherapy for mUC or in perioperative setting (progression within 12 mo) and Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2...
May 2018: European Urology
https://www.readbyqxmd.com/read/29423515/atezolizumab-mpdl3280a-monotherapy-for-patients-with-metastatic-urothelial-cancer-long-term-outcomes-from-a-phase-1-study
#8
Daniel P Petrylak, Thomas Powles, Joaquim Bellmunt, Fadi Braiteh, Yohann Loriot, Rafael Morales-Barrera, Howard A Burris, Joseph W Kim, Beiying Ding, Constanze Kaiser, Marcella Fassò, Carol O'Hear, Nicholas J Vogelzang
Importance: Atezolizumab (anti-programmed death ligand 1) has demonstrated safety and activity in advanced and metastatic urothelial carcinoma, but its long-term clinical profile remains unknown. Objective: To report long-term clinical outcomes with atezolizumab therapy for patients with metastatic urothelial carcinoma. Design, Setting, and Participants: Patients were enrolled in an expansion cohort of an ongoing, open-label, phase 1 study...
April 1, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29353553/change-in-neutrophil-to-lymphocyte-ratio-nlr-in-response-to-immune-checkpoint-blockade-for-metastatic-renal-cell-carcinoma
#9
Aly-Khan A Lalani, Wanling Xie, Dylan J Martini, John A Steinharter, Craig K Norton, Katherine M Krajewski, Audrey Duquette, Dominick Bossé, Joaquim Bellmunt, Eliezer M Van Allen, Bradley A McGregor, Chad J Creighton, Lauren C Harshman, Toni K Choueiri
BACKGROUND: An elevated Neutrophil-to-lymphocyte ratio (NLR) is associated with worse outcomes in several malignancies. However, its role with contemporary immune checkpoint blockade (ICB) is unknown. We investigated the utility of NLR in metastatic renal cell carcinoma (mRCC) patients treated with PD-1/PD-L1 ICB. METHODS: We examined NLR at baseline and 6 (±2) weeks later in 142 patients treated between 2009 and 2017 at Dana-Farber Cancer Institute (Boston, USA)...
January 22, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29277584/comparative-effectiveness-of-robot-assisted-vs-open-radical-cystectomy
#10
Nawar Hanna, Jeffrey J Leow, Maxine Sun, David F Friedlander, Thomas Seisen, Firas Abdollah, Stuart R Lipsitz, Mani Menon, Adam S Kibel, Joaquim Bellmunt, Toni K Choueiri, Quoc-Dien Trinh
OBJECTIVES: Over the past decade, robot-assisted radical cystectomy (RARC) has gained traction as an alternative to the conventional open approach open radical cystectomy (ORC). However, the benefits of RARC over ORC remain unclear. Our objective was to conduct a comparative effectiveness analysis between RARC and ORC using data from the National Cancer Data Base. MATERIALS AND METHODS: Within the National Cancer Data Base, we identified patients with localized muscle-invasive bladder cancer who underwent RC between 2010 and 2013...
March 2018: Urologic Oncology
https://www.readbyqxmd.com/read/29259186/mutational-patterns-in-chemotherapy-resistant-muscle-invasive-bladder-cancer
#11
David Liu, Philip Abbosh, Daniel Keliher, Brendan Reardon, Diana Miao, Kent Mouw, Amaro Weiner-Taylor, Stephanie Wankowicz, Garam Han, Min Yuen Teo, Catharine Cipolla, Jaegil Kim, Gopa Iyer, Hikmat Al-Ahmadie, Essel Dulaimi, David Y T Chen, R Katherine Alpaugh, Jean Hoffman-Censits, Levi A Garraway, Gad Getz, Scott L Carter, Joaquim Bellmunt, Elizabeth R Plimack, Jonathan E Rosenberg, Eliezer M Van Allen
Despite continued widespread use, the genomic effects of cisplatin-based chemotherapy and implications for subsequent treatment are incompletely characterized. Here, we analyze whole exome sequencing of matched pre- and post-neoadjuvant cisplatin-based chemotherapy primary bladder tumor samples from 30 muscle-invasive bladder cancer patients. We observe no overall increase in tumor mutational burden post-chemotherapy, though a significant proportion of subclonal mutations are unique to the matched pre- or post-treatment tumor, suggesting chemotherapy-induced and/or spatial heterogeneity...
December 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/29219016/pembrolizumab-in-the-treatment-of-advanced-urothelial-cancer
#12
Kevin T Lundgren, Matthew S Farina, Joaquim Bellmunt
Pembrolizumab is a humanized monoclonal antibody that targets PD-1. In the Phase III trial KEYNOTE-045, pembrolizumab was associated with a significant overall survival benefit when compared with docetaxel, paclitaxel and vinflunine in second line metastatic urothelial carcinoma (UC). Additionally, in the first line, early results from an interim analysis of the Phase II trial Keynote-052 study indicated that pembrolizumab is efficacious for cisplatin-ineligible patients. Based on data from these trials, pembrolizumab was the most recent among the five checkpoint inhibitors tested in UC to be approved by the US FDA in May 2017...
December 2017: Future Oncology
https://www.readbyqxmd.com/read/29203837/urothelial-cancer-in-2017-changes-in-expectations-for-metastatic-urothelial-carcinoma
#13
Joaquim Bellmunt, Rosa Nadal
No abstract text is available yet for this article.
February 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29198325/ercc1-as-a-prognostic-factor-for-survival-in-patients-with-advanced-urothelial-cancer-treated-with-platinum-based-chemotherapy-a-systematic-review-and-meta-analysis
#14
REVIEW
Yuksel Urun, Jeffrey J Leow, Andre P Fay, Laurence Albiges, Toni K Choueiri, Joaquim Bellmunt
BACKGROUND: The predictive role of excision repair cross-complementing group 1 (ERCC1) as a predictive factor in patients with advanced urothelial cancer (AUC) treated with platinum-based treatment is not well defined. Here, we evaluate the role of ERCC1 in patients with AUC treated with platinum-based treatment. METHODS: We performed comprehensive, systematic computerized search to identify relevant studies through Medline, Embase, Cochrane Controlled Trials Register (CCTR) databases and abstracts from American Society of Clinical Oncology (ASCO) and ASCO Genitourinary Cancers Symposium, European Society For Medical Oncology (ESMO) and European Association of Urology (EAU) meeting up to July 2015...
December 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29158104/impact-of-primary-tumor-location-on-survival-from-the-european-organization-for-the-research-and-treatment-of-cancer-advanced-urothelial-cancer-studies
#15
Marco Moschini, Shahrokh F Shariat, Morgan Rouprêt, Maria De Santis, Joaquim Bellmunt, Cora N Sternberg, Bertrand Tombal, Laurence Collette
PURPOSE: The prognostic relevance of primary location of urothelial carcinoma on survival has been poorly investigated. MATERIALS AND METHODS: We used prospectively collected data from 3 European Organization for the Research and Treatment of Cancer advanced urothelial carcinoma studies, including 30924 (methotrexate, vinblastine, doxorubicin and cisplatin vs high dose methotrexate, vinblastine, doxorubicin and cisplatin), 30986 (methotrexate, carboplatin and vinblastine vs gemcitabine and cisplatin in patients who were not candidates for cisplatin) and 30987 (gemcitabine and cisplatin-paclitaxel vs gemcitabine and cisplatin in candidates for cisplatin)...
May 2018: Journal of Urology
https://www.readbyqxmd.com/read/29158079/bone-metastases-as-the-only-metastatic-site-in-patients-with-urothelial-carcinoma-focus-on-a-special-patient-population
#16
Andrea Necchi, Gregory R Pond, Sumanta K Pal, Neeraj Agarwal, Daniel W Bowles, Elizabeth R Plimack, Evan Y Yu, Sylvain Ladoire, Jack Baniel, Simon Crabb, Gunter Niegisch, Sandy Srinivas, Dominik R Berthold, Jonathan E Rosenberg, Thomas Powles, Aristotelis Bamias, Lauren C Harshman, Joaquim Bellmunt, Matthew D Galsky
BACKGROUND: Patients with exclusive bone metastatic spread from urothelial carcinoma (UC) throughout their disease course represent a rare subgroup with unique clinical features. These patients deserved special consideration in a retrospective multicenter study. PATIENTS AND METHODS: Analyses were made from a pool of 1911 patients with a diagnosis of metastatic UC, from 23 centers. Baseline characteristics, access to treatment, and outcomes were analyzed according to metastatic spread...
November 1, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29137449/differential-side-effects-profile-in-patients-with-mcrpc-treated-with-abiraterone-or-enzalutamide-a-meta-analysis-of-randomized-controlled-trials
#17
REVIEW
Raphael B Moreira, Marcio Debiasi, Edoardo Francini, Pier V Nuzzo, Guillermo De Velasco, Fernando C Maluf, Andre P Fay, Joaquim Bellmunt, Toni K Choueiri, Fabio A Schutz
Background: Abiraterone and enzalutamide are currently approved for mCRPC patients. Both drugs have distinct mechanisms of action and may have different toxicity profile. There are limited data comparing the side effects of abiraterone and enzalutamide. We performed a meta-analysis of randomized controlled trials (RCT) to better characterize the risk of adverse events associated with both drugs. Methods: We performed a literature search on MEDLINE for studies reporting abiraterone and enzalutamide side effects from January 1966 to July 31, 2015...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29121502/the-prognostic-role-of-epigenetic-dysregulation-in-bladder-cancer-a-systematic-review
#18
REVIEW
David Casadevall, Anaïs Yacine Kilian, Joaquim Bellmunt
BACKGROUND: Despite adequate treatment and follow-up, around one fifth of patients with localized bladder cancer will present with disease progression. Adequate prognostic biomarkers are lacking to define patients who are at risk. Mutations in chromatin remodeling genes are more frequently found in bladder cancer than in any other solid tumor. However, the prognostic relevance of epigenetic dysregulation has not been established and may offer an opportunity for biomarker discovery. METHODS: Looking for prognostic epigenetic factors, we performed a comprehensive PubMed search using keywords such as "bladder cancer", "chromatin remodeling", "gene methylation" and "epigenetics"...
December 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28988769/comprehensive-molecular-characterization-of-muscle-invasive-bladder-cancer
#19
A Gordon Robertson, Jaegil Kim, Hikmat Al-Ahmadie, Joaquim Bellmunt, Guangwu Guo, Andrew D Cherniack, Toshinori Hinoue, Peter W Laird, Katherine A Hoadley, Rehan Akbani, Mauro A A Castro, Ewan A Gibb, Rupa S Kanchi, Dmitry A Gordenin, Sachet A Shukla, Francisco Sanchez-Vega, Donna E Hansel, Bogdan A Czerniak, Victor E Reuter, Xiaoping Su, Benilton de Sa Carvalho, Vinicius S Chagas, Karen L Mungall, Sara Sadeghi, Chandra Sekhar Pedamallu, Yiling Lu, Leszek J Klimczak, Jiexin Zhang, Caleb Choo, Akinyemi I Ojesina, Susan Bullman, Kristen M Leraas, Tara M Lichtenberg, Catherine J Wu, Nicholaus Schultz, Gad Getz, Matthew Meyerson, Gordon B Mills, David J McConkey, John N Weinstein, David J Kwiatkowski, Seth P Lerner
We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival "neuronal" subtype in which the majority of tumors lacked small cell or neuroendocrine histology...
October 19, 2017: Cell
https://www.readbyqxmd.com/read/28967485/first-line-pembrolizumab-in-cisplatin-ineligible-patients-with-locally-advanced-and-unresectable-or-metastatic-urothelial-cancer-keynote-052-a-multicentre-single-arm-phase-2-study
#20
RANDOMIZED CONTROLLED TRIAL
Arjun V Balar, Daniel Castellano, Peter H O'Donnell, Petros Grivas, Jacqueline Vuky, Thomas Powles, Elizabeth R Plimack, Noah M Hahn, Ronald de Wit, Lei Pang, Mary J Savage, Rodolfo F Perini, Stephen M Keefe, Dean Bajorin, Joaquim Bellmunt
BACKGROUND: More than half of all patients with advanced urothelial cancer cannot receive standard, first-line cisplatin-based chemotherapy because of renal dysfunction, poor performance status, or other comorbidities. We assessed the activity and safety of first-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer. METHODS: In this multicentre, single-arm, phase 2 study (KEYNOTE-052), cisplatin-ineligible patients with advanced urothelial cancer who had not been previously treated with systemic chemotherapy were recruited from 91 academic medical centres in 20 countries...
November 2017: Lancet Oncology
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