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Pembrolizumab and urothelial

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https://www.readbyqxmd.com/read/30304985/updates-and-novel-treatments-in-urothelial-carcinoma
#1
Kirollos S Hanna
Urothelial Carcinoma (UC) is the second most common malignancy of the genitourinary system and is the sixth most common cancer in the USA. Over a decade prior to 2016, the standard of care for early disease consisted of transuretheral resection of the bladder tumor with or without intravesicular chemotherapy or immunotherapy. Systemic chemotherapies such as gemcitabine and cisplatin combinations or dose-dense methotrexate, vinblastine, doxorubicin, cisplatin were reserved for recurrent, muscle-invasive, advanced or metastatic disease...
October 10, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/30304963/nivolumab-for-the-treatment-of-hepatocellular-carcinoma
#2
Fabian Finkelmeier, Oliver Waidmann, Joerg Trojan
T-cell checkpoint inhibition as a cancer treatment approach has been the main breakthrough in cancer treatment during the last years. Since the approval of the first commercial CTLA-4 antibody ipilimumab in 2011 for the treatment of melanoma, research and drug development in this field has accelerated massively. In 2014 the US Food and Drug Administration (FDA) approved the first PD-1 targeting agent, namely pembrolizumab, shortly followed by nivolumab. Areas covered: Nivolumab is a fully human immunoglobulin G4 anti-PD-1 monoclonal antibody which is approved for multiple advanced malignancies, including melanoma, non-small cell lung cancer, renal cell cancer, Hodgkin's lymphoma, squamous head and neck cancer and urothelial carcinoma...
October 10, 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/30275703/pd1-pdl1-inhibitors-for-the-treatment-of-advanced-urothelial-bladder-cancer
#3
REVIEW
David D Stenehjem, Dao Tran, Michael A Nkrumah, Shilpa Gupta
Introduction: Until recently, systemic chemotherapy was the only option for treating bladder cancer and outcomes remained dismal. After a long gap of no progress for 40 years, immuno-therapy with checkpoint inhibitors (PDL1 and PD1) has revolutionized the treatment paradigm of bladder cancer, with five approved agents to treat platinum-refractory bladder cancer since the first approval of atezolizumab in May 2016. Methods: This review summarizes the most recent data on approved checkpoint inhibitors currently used in management of advanced bladder cancer...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/30267200/immunological-correlates-of-response-to-immune-checkpoint-inhibitors-in-metastatic-urothelial-carcinoma
#4
Alice Tzeng, C Marcela Diaz-Montero, Patricia A Rayman, Jin S Kim, Paul G Pavicic, James H Finke, Pedro C Barata, Marcelo Lamenza, Sarah Devonshire, Kim Schach, Hamid Emamekhoo, Marc S Ernstoff, Christopher J Hoimes, Brian I Rini, Jorge A Garcia, Timothy D Gilligan, Moshe C Ornstein, Petros Grivas
BACKGROUND: The identification of prognostic and/or predictive biomarkers for response to immune checkpoint inhibitors (ICI) could help guide treatment decisions. OBJECTIVE: We assessed changes in programmed cell death-1 (PD1)/PD1 ligand (PDL1) expression in key immunomodulatory cell subsets (myeloid-derived suppressor cells [MDSC]; cytotoxic T lymphocytes [CTL]) following ICI therapy and investigated whether these changes correlated with outcomes in patients with metastatic urothelial carcinoma (mUC)...
October 2018: Targeted Oncology
https://www.readbyqxmd.com/read/30265610/epacadostat-plus-pembrolizumab-in-patients-with-advanced-solid-tumors-phase-i-results-from-a-multicenter-open-label-phase-i-ii-trial-echo-202-keynote-037
#5
Tara C Mitchell, Omid Hamid, David C Smith, Todd M Bauer, Jeffrey S Wasser, Anthony J Olszanski, Jason J Luke, Ani S Balmanoukian, Emmett V Schmidt, Yufan Zhao, Xiaohua Gong, Janet Maleski, Lance Leopold, Thomas F Gajewski
PURPOSE: Tumors may evade immunosurveillance through upregulation of the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme. Epacadostat is a potent and highly selective IDO1 enzyme inhibitor. The open-label phase I/II ECHO-202/KEYNOTE-037 trial evaluated epacadostat plus pembrolizumab, a programmed death protein 1 inhibitor, in patients with advanced solid tumors. Phase I results on maximum tolerated dose, safety, tolerability, preliminary antitumor activity, and pharmacokinetics are reported...
September 28, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/30253680/health-related-quality-of-life-in-cancer-patients-treated-with-pd-l-1-inhibitors-a-systematic-review
#6
Omar Abdel-Rahman, Hani Oweira, Anwar Giryes
A systematic review was performed to explore the health-related quality of life (HRQoL) outcomes among cancer patients receiving PD-(L)1 inhibitors compared to those receiving traditional cytotoxic therapy. Areas covered: Citations from PubMed and the American Society of Clinical Oncology meeting library were examined. Cross-references from original studies and review articles were also reviewed. Eligible trials included randomized controlled trials of cancer patients treated with one of the PD-(L)1 inhibitors and reporting HRQoL outcomes...
September 26, 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/30208947/alpha-fetoprotein-afp-as-tumor-marker-in-a-patient-with-urothelial-cancer-with-exceptional-response-to-anti-pd-1-therapy-and-an-escape-lesion-mimic
#7
Johannes C Melms, Rohit Thummalapalli, Kristin Shaw, Huihui Ye, Leo Tsai, Rupal S Bhatt, Benjamin Izar
The development of a new lesion in a patient with a complete remission to anti-PD-1 therapy is highly concerning for a drug resistant escape lesion. Here, we present a case of a 62-year-old patient with chemotherapy-resistant metastatic urothelial cancer who had a complete remission to pembrolizumab. The patient's disease burden tracked closely to serum levels of alpha-fetoprotein (AFP) expressed by the tumor and served as an accurate tumor marker. Surveillance imaging revealed a solitary growing pulmonary nodule mimicking an escape lesion in the absence of an increase in AFP levels...
September 12, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/30182073/immune-checkpoint-inhibitors-for-urothelial-carcinoma
#8
REVIEW
Hyung Suk Kim, Ho Kyung Seo
Urothelial carcinoma (UC), originating in the bladder or upper urinary tract, is the most common histological type of cancer. Currently, platinum-based cytotoxic chemotherapy is the standard treatment for metastatic UC (mUC) and the preferred treatment option in the perioperative (neoadjuvant and/or adjuvant) setting of muscle invasive bladder cancer (MIBC). In addition, intravesical bacillus Calmette-Guerin immunotherapy or chemotherapy is applied as the adjuvant therapeutic option in non-muscle invasive bladder cancer (NMIBC) after transurethral resection, to prevent recurrence and progression...
September 2018: Investigative and Clinical Urology
https://www.readbyqxmd.com/read/30166228/pembrolizumab-combined-with-either-docetaxel-or-gemcitabine-in-patients-with-advanced-or-metastatic-platinum-refractory-urothelial-cancer-results-from-a-phase-i-study
#9
Mamta Parikh, Chong-Xian Pan, Laurel A Beckett, Yueju Li, Daniel A Robles, Pawandeep K Aujla, Primo N Lara
INTRODUCTION: Cytotoxic chemotherapy might prime urothelial cancer (UC) to checkpoint inhibition, prompting a trial of chemotherapy with the programmed death receptor-1 inhibitor pembrolizumab. PATIENTS AND METHODS: Patients with advanced, platinum-refractory UC received pembrolizumab and either docetaxel (arm A) or gemcitabine (arm B). Primary end points were assessments of maximum tolerated dose and dose-limiting toxicity (DLT). Secondary end points were overall response rate (ORR) and progression-free survival (PFS)...
July 12, 2018: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/30083254/approved-checkpoint-inhibitors-in-bladder-cancer-which-drug-should-be-used-when
#10
REVIEW
Pooja Ghatalia, Matthew Zibelman, Daniel M Geynisman, Elizabeth Plimack
The treatment of advanced metastatic urothelial carcinoma has recently evolved with the approval of five checkpoint inhibitors. In the second-line setting, in patients who have progressed on cisplatin-based chemotherapy, pembrolizumab, atezolizumab, durvalumab, nivolumab and avelumab are United States Food and Drug Administration (FDA) approved. In cisplatin-ineligible patients, atezolizumab and pembrolizumab are the FDA-approved checkpoint inhibitors. Here we describe the updated clinical efficacy of these checkpoint inhibitors in the treatment of advanced urothelial carcinoma and then suggest how they can be sequenced in the context of available chemotherapeutic options...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/30036453/pembrolizumab-monotherapy-versus-chemotherapy-for-treatment-of-advanced-urothelial-carcinoma-with-disease-progression-during-or-following-platinum-containing-chemotherapy-a-cochrane-rapid-review
#11
REVIEW
Vikram Narayan, Andreas Kahlmeyer, Philipp Dahm, Nicole Skoetz, Michael C Risk, Connie Bongiorno, Neil Patel, Eu Chang Hwang, Jae Hung Jung, Gerald Gartlehner, Frank Kunath
BACKGROUND: The use of systemic immunotherapy targets is emerging as an important treatment option for metastatic urothelial carcinoma, particularly for patients who cannot tolerate or who fail cisplatin-based chemotherapy. One such target is the inhibition of the checkpoint protein programmed cell death-1 (PD-1) receptor and its ligand (PD-L1) by monoclonal antibodies. OBJECTIVES: To assess the effects of pembrolizumab monotherapy versus chemotherapy for treatment of advanced urothelial carcinoma with disease progression during or following platinum-containing chemotherapy...
July 23, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/30030817/pembrolizumab-for-previously-treated-advanced-or-metastatic-urothelial-cancer-an-evidence-review-group-perspective-of-a-nice-single-technology-appraisal
#12
REVIEW
Daniel Gallacher, Xavier Armoiry, Peter Auguste, Rachel Court, Theodoros Mantopoulos, Jacoby Patterson, Maria De Santis, Joanne Cresswell, Hema Mistry
Pembrolizumab is an intravenously administered monoclonal antibody licensed for locally advanced or metastatic urothelial carcinoma after platinum-containing chemotherapy. This summary presents the perspective of Warwick Evidence, the Evidence Review Group (ERG) appointed by the National Institute of Health and Care Excellence (NICE) for the single technology appraisal of pembrolizumab for this indication. Pembrolizumab is manufactured by Merck, Sharp and Dohme (MSD). The major source of clinical effectiveness was the KEYNOTE-045 trial, where 542 patients received either pembrolizumab or clinician's choice of docetaxel, paclitaxel or vinflunine as a second-line treatment...
July 21, 2018: PharmacoEconomics
https://www.readbyqxmd.com/read/30021426/immune-check-point-inhibitors-for-metastatic-urothelial-carcinoma-current-evidence-based-approach-for-urology-daily-practice
#13
Nikita D Nabar, Maximilian P Brandt, Christian Thomas, Igor Tsaur, Georg Bartsch, Wolfgang Jaeger, Axel Haferkamp, Thomas Höfner
INTRODUCTION: Treatment strategy for inoperable and metastatic urothelial carcinoma (mUC) has been revolutionized by the introduction of programmed cell death protein 1 (PD-1) and programmed cell death protein ligand (PD-L1) antibodies. During the last 3 decades treatment options were limited to chemotherapy, making further treatment of patients whose disease progressed under ongoing therapy or who were ineligible to receive cytotoxic therapy in the first place, nearly impossible. EVIDENCE ACQUISITION: Five antibodies including pembrolizumab (PD-L1 antibody), atezolizumab (PD-1 antibody), nivolumab (PD-1 antibody), avelumab and durvalumab (PDL1 antibodies) have been approved in the treatment of advanced urothelial carcinoma in firstand second-line treatment setting...
July 18, 2018: Minerva Urologica e Nefrologica, the Italian Journal of Urology and Nephrology
https://www.readbyqxmd.com/read/30012528/dose-limiting-urinary-toxicity-with-pembrolizumab-combined-with-weekly-hypofractionated-radiation-therapy-in-bladder-cancer
#14
Alison Claire Tree, Kelly Jones, Shaista Hafeez, Mansour Taghavi Azar Sharabiani, Kevin Joseph Harrington, Susan Lalondrelle, Merina Ahmed, Robert Anthony Huddart
There is currently significant interest in the potential benefits of combining radiation and immune checkpoint blockade (ICB) to stimulate both regional and distant abscopal immune responses. In melanoma and lung cancer, patients who have received radiation therapy during ICB appear to have prolonged survival. The PLUMMB trial (Pembrolizumab in Muscle-invasive/Metastatic Bladder cancer) (NCT02560636) is a phase I study to test the tolerability of a combination of weekly radiation therapy with pembrolizumab in patients with metastatic or locally advanced urothelial cancer of the bladder...
August 1, 2018: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/30002656/biomarkers-for-clinical-benefit-of-immune-checkpoint-inhibitor-treatment-a-review-from-the-melanoma-perspective-and-beyond
#15
REVIEW
Kristina Buder-Bakhaya, Jessica C Hassel
Background: Immune checkpoint inhibition (ICI) with anti-CTLA-4 and/or anti-PD-1 antibodies is standard treatment for metastatic melanoma. Anti-PD-1 (pembrolizumab, nivolumab) and anti-PD-L1 antibodies (atezolizumab, durvalumab, and avelumab) have been approved for treatment of several other advanced malignancies, including non-small-cell lung cancer (NSCLC); renal cell, and urothelial carcinoma; head and neck cancer; gastric, hepatocellular, and Merkel-cell carcinoma; and classical Hodgkin lymphoma...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29985683/pembrolizumab-and-epacadostat-induced-fatal-myocarditis-and-myositis-presenting-as-a-case-of-ptosis-and-ophthalmoplegia
#16
Justin B Hellman, Ilana Traynis, Lily Koo Lin
We report the first case of fatal myocarditis presenting as bilateral ptosis in a patient on combination therapy with pembrolizumab and epacadostat. An 83 year-old man with stage III high-grade urothelial carcinoma presented with acute onset droopy eyelids one month after starting pembrolizumab and epacadostat. Exam showed myogenic ptosis and ophthalmoplegia. He was later found to have acute myocarditis with complete heart block and subsequently passed away. Pembrolizumab in combination with epacadostat can induce a potentially fatal myocarditis...
July 9, 2018: Orbit
https://www.readbyqxmd.com/read/29935800/developments-in-urologic-oncology-oncoforum-the-best-of-2017
#17
F Gómez-Veiga, A Alcaraz-Asensio, J Burgos-Revilla, J Cózar-Olmo
OBJECTIVE: To put forth new findings of urologic oncology with impact on clinical practice presented during 2017 in the main annual meetings. METHODS: This document reviews abstracts on prostate, kidney and bladder cancer presented at the congresses of 2016 (EAU, AUA, ASCO, ESMO and ASTRO) and publications with the highest impact in this period valued with the highest scores by the OncoForum committee. RESULTS: Among patients at high risk of recurrent renal cell carcinoma after nephrectomy, adjuvant sunitinib compared to placebo showed a benefit in patients at higher risk of recurrence...
October 2018: Actas Urologicas Españolas
https://www.readbyqxmd.com/read/29909921/myositis-as-an-adverse-event-of-immune-checkpoint-blockade-for-cancer-therapy
#18
Mohsin Shah, Jean H Tayar, Noha Abdel-Wahab, Maria E Suarez-Almazor
OBJECTIVES: Immune checkpoint inhibitors (ICIs) can successfully treat cancer, but their use can be hindered by serious immune-related adverse events. We report six patients receiving ICIs who presented with de novo myositis. METHODS: We identified patients with myositis who were receiving ICIs between January 2004 and September 2016 at The University of Texas MD Anderson Cancer Center. RESULTS: Six patients developed de novo myositis. The mean age was 64...
May 18, 2018: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/29784744/the-changing-treatment-landscape-for-metastatic-urothelial-carcinoma
#19
Thomas W Flaig
Urothelial carcinoma is the predominant histologic type of bladder cancer. After 30 years of minimal progress in the treatment of advanced-stage disease, recent advances in the genomic characterization of urothelial cancer and breakthroughs in bladder cancer therapeutics have rejuvenated the field. Nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab are among the exciting recent novel therapeutic advances gaining approvals by the FDA for treatment of advanced-stage urothelial carcinoma. Yet the challenge for clinicians is to determine the optimal choice of agents as first-line or second-line therapy and which offers the best chance for overall survival for the individual patient in this rapidly changing field...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29663063/-treatment-with-pd-1-pd-l1-and-ctla-4-immune-checkpoint-inhibitors-immune-mediated-side-effects
#20
REVIEW
M-O Grimm, H Oppel-Heuchel, S Foller
Immune checkpoint inhibitors are a new standard therapy for advanced or metastatic urothelial as well as renal cell carcinoma. Atezolizumab and Pembrolizumab have been approved for the treatment of cisplatin-ineligible patients with transitional call cancer in the 1st line setting; both antibodies and Nivolumab may also be used after platinum based prior therapy. Regarding renal cell carcinoma approval for 1st line treatment with the combination of Nivolumab and Ipilimumab for patients at intermediate or high risk (IMDC) is currently expected...
May 2018: Der Urologe. Ausg. A
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