Read by QxMD icon Read

Pembrolizumab and urothelial

Margaret Ottaviano, Sabino De Placido, Paolo Antonio Ascierto
AbstractSeveral researches have been carried over the last few decades to understand of how cancer evades the immune system and thus to identify therapies that could directly act on patient's immune system in the way of restore or induce a response to cancer. As a consequence, "cancer immunotherapy" is conquering predominantly the modern scenario of the fight against cancer. The recent clinical success of immune checkpoint inhibitors (ICIs) has created an entire new class of anti-cancer drugs and restored interest in the field of immuno-oncology, leading to regulatory approvals of several agents for the treatment of a variety of malignancies...
February 12, 2019: Virchows Archiv: An International Journal of Pathology
David J Einstein, Guru Sonpavde
Cisplatin has been established as an important agent in the neoadjuvant setting prior to radical cystectomy (RC) surgery for muscle-invasive urothelial cancer (MIUC) as well as in the unresectable or metastatic urothelial carcinoma (mUC) setting. Unfortunately, many patients in practice are felt to be "cisplatin-ineligible." Thus, it is vital that we develop treatment approaches and novel therapeutics for this population. We evaluate therapeutic alternatives to cisplatin-based treatment. For patients undergoing RC, there is no recommended alternative to neoadjuvant cisplatin-based combination therapy, and upfront RC or clinical trials are preferable...
February 11, 2019: Current Treatment Options in Oncology
J Rogado, J M Sánchez-Torres, N Romero-Laorden, A I Ballesteros, V Pacheco-Barcia, A Ramos-Leví, R Arranz, A Lorenzo, P Gullón, O Donnay, M Adrados, P Costas, J Aspa, A Alfranca, R Mondéjar, R Colomer
BACKGROUND: Cancer immune therapy has shown remarkable benefit in the treatment of a range of cancer types, although it may initiate autoimmune-related disorders in some patients. We have attempted to establish whether the incidence of irAEs after the use of anti-PD-1 antibodies nivolumab or pembrolizumab in advanced malignancies is associated with anti-PD-1 treatment efficacy. PATIENTS AND METHODS: We studied patients treated with single-agent nivolumab or pembrolizumab for advanced cancer...
January 22, 2019: European Journal of Cancer
Nora Sundahl, Gillian Vandekerkhove, Karel Decaestecker, Annabel Meireson, Pieter De Visschere, Valérie Fonteyne, Daan De Maeseneer, Dries Reynders, Els Goetghebeur, Jo Van Dorpe, Sofie Verbeke, Matti Annala, Lieve Brochez, Kim Van der Eecken, Alexander W Wyatt, Sylvie Rottey, Piet Ost
Preclinical data indicate that radiotherapy works synergistically with pembrolizumab, but the effect and toxicity of this combination may depend on radiotherapy timing. We conducted a randomized phase 1 trial combining pembrolizumab with either sequential (A) or concomitant (B) stereotactic body radiotherapy (SBRT) in metastatic urothelial carcinoma (mUC). No dose-limiting toxicity occurred. Treatment-related adverse events (trAEs; Common Terminology Criteria for Adverse Events v4.0) of grade 1-2 occurred in six of nine and all nine patients in arms A and B, respectively...
January 19, 2019: European Urology
Maxime Chénard-Poirier, Elizabeth C Smyth
Immune checkpoint blockade has revolutionised the treatment of multiple cancers including melanoma, non-small cell lung cancer, urothelial and renal cell cancers. For patients with chemorefractory gastroesophageal cancer, treatment with anti-PD-1 therapy results in modest benefits in overall survival; nivolumab and pembrolizumab have been licenced in Japan and the USA, respectively, for this indication. However, initial enthusiasm has been tempered by the results of several large negative trials; immune checkpoint blockade is not superior to chemotherapy in the second-line setting or beyond in unselected or low PD-L1-expressing patients...
January 2, 2019: Drugs
Xin Rui, Ting-Ting Gu, Hua-Feng Pan, Hui-Zhi Zhang
INTRODUCTION: Newly published results of clinical trials has demonstrated immune checkpoint inhibitors as robust antitumor agents for urothelial carcinoma patients. However, searching for predictive biomarkers is still on the way. Previous clinical trials used PD-L1 as biomarkers, however, whether it can predict the objective response rate and overall survival is controversial. This is the first and latest study to pool the newest data in order the evaluate PD-L1 biomarker. RESULT: Nine studies were included and 1,436 urothelial carcinoma patients were included...
February 2019: International Immunopharmacology
A González Del Alba, G De Velasco, N Lainez, P Maroto, R Morales-Barrera, J Muñoz-Langa, B Pérez-Valderrama, L Basterretxea, C Caballero, S Vazquez
The goal of this article is to provide recommendations about the management of muscle-invasive (MIBC) and metastatic bladder cancer. New molecular subtypes of MIBC are associated with specific clinical-pathological characteristics. Radical cystectomy and lymph node dissection are the gold standard for treatment and neoadjuvant chemotherapy with a cisplatin-based combination should be recommended in fit patients. The role of adjuvant chemotherapy in MIBC remains controversial; its use must be considered in patients with high-risk who are able to tolerate a cisplatin-based regimen, and have not received neoadjuvant chemotherapy...
December 18, 2018: Clinical & Translational Oncology
D Wilborn, S Schmidt
No abstract text is available yet for this article.
December 17, 2018: Der Urologe. Ausg. A
Rohit K Jain, Travis Snyders, Lakshminarayanan Nandgoapal, Rohan Garje, Yousef Zakharia, Shilpa Gupta
Checkpoint inhibitors have monumentally transformed the treatment of metastatic urothelial carcinoma. While the efficacy and safety of the different agents are similar in platinum-refractory metastatic urothelial carcinoma, pembrolizumab is the only agent that was superior to chemotherapy in a randomized phase III trial. Pembrolizumab and atezolizumab are also approved as first-line therapies in cisplatin-ineligible metastatic urothelial carcinoma. Several immunotherapy trials are ongoing in non-metastatic setting to maximize responses upfront...
December 15, 2018: Current Treatment Options in Oncology
Shijie Ren, Hazel Squires, Emma Hock, Eva Kaltenthaler, Andrew Rawdin, Constantine Alifrangis
As part of its Single Technology Appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (Merck Sharp & Dohme) of pembrolizumab (Keytruda® ) to submit evidence of its clinical and cost effectiveness for the treatment of locally advanced or metastatic urothelial cancer where cisplatin is unsuitable. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG)...
December 13, 2018: PharmacoEconomics
Daniel L Suzman, Sundeep Agrawal, Yang-Min Ning, V Ellen Maher, Laura L Fernandes, Stella Karuri, Shenghui Tang, Rajeshwari Sridhara, Jason Schroeder, Kirsten B Goldberg, Amna Ibrahim, Amy E McKee, Richard Pazdur, Julia A Beaver
The U.S. Food and Drug Administration (FDA) granted accelerated approval to atezolizumab and pembrolizumab in April and May 2017, respectively, for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy. These approvals were based on efficacy and safety data demonstrated in the two single-arm trials, IMvigor210 (atezolizumab) and KEYNOTE-052 (pembrolizumab). The primary endpoint, confirmed objective response rate, was 23...
December 12, 2018: Oncologist
Markus Eckstein, Philipp Erben, Maximilian C Kriegmair, Thomas S Worst, Cleo-Aron Weiß, Ralph M Wirtz, Sven Wach, Robert Stoehr, Danijel Sikic, Carol I Geppert, Veronika Weyerer, Simone Bertz, Johannes Breyer, Wolfgang Otto, Bastian Keck, Maximilian Burger, Helge Taubert, Wilko Weichert, Bernd Wullich, Christian Bolenz, Arndt Hartmann, Franziska Erlmeier
BACKGROUND: Recently, the Food and Drug Administration (FDA)/European Medicines Agency (EMA) restricted first-line use of atezolizumab and pembrolizumab in patients with metastasised urothelial carcinoma by defining distinct programmed cell death ligand-1 cut-offs. We analysed the diagnostic performance of all FDA/EMA-approved programmed cell death ligand-1 assays with emphasis on new restrictions for first-line treatment with atezolizumab and pembrolizumab. PATIENTS AND METHODS: Two hundred fifty-one urothelial carcinomas were analysed on tissue microarrays with four cores of each tumour...
December 5, 2018: European Journal of Cancer
Steven D Criss, Davis T Weaver, Deirdre F Sheehan, Richard J Lee, Pari V Pandharipande, Chung Yin Kong
PURPOSE: Our purpose was to evaluate the effect of PD-L1 testing on the cost-effectiveness of pembrolizumab for second-line treatment of advanced urothelial carcinoma in the bladder from the U.S. societal perspective. MATERIALS AND METHODS: We developed a microsimulation model to compare 3 treatment strategies: (1) treat all patients with standard-of-care chemotherapy, (2) treat all patients with pembrolizumab, and (3) treat patients with PD-L1-positive tumors at a ≥1% expression threshold with pembrolizumab, and all others with standard-of-care chemotherapy...
December 6, 2018: Urologic Oncology
Saby George, Antonios Papanicolau-Sengos, Felicia L Lenzo, Jeffrey M Conroy, Mary Nesline, Sarabjot Pabla, Sean T Glenn, Blake Burgher, Jonathan Andreas, Vincent Giamo, Moachun Qin, Yirong Wang, Lorenzo Galluzzi, Carl Morrison
We report the immunological profile of a patient with upper-tract urothelial carcinoma experiencing stable disease on pembrolizumab for 20 months. The tumor exhibited extensive infiltration by CD8+ cytotoxic T lymphocytes, low-to-moderate mutational burden, no PD-L1 staining by commercially available immunohistochemical assays, but amplification of CD274 (coding for PD-L1) and/or PDCD1LG2 (encoding PD-L2) by fluorescence in situ hybridization. RNA-seq revealed multiple biomarkers of an ongoing immune response and compensatory immune evasion, including moderate PD-L1 levels coupled with robust PD-L2 expression...
2018: Oncoimmunology
Di Maria Jiang, Srikala S Sridhar
BACKGROUND: Metastatic urothelial cancer (UC) is a lethal disease. Until 2016, cytotoxic chemotherapy with substantial toxicity was the only therapeutic option. In the first-line metastatic setting, cisplatin-based combination chemotherapy remains the standard of care. For cisplatin-ineligible patients, carboplatin-based regimens that are less efficacious are often substituted. In platinum-refractory patients, taxanes and vinflunine are the most commonly used. Recently, treatment options have largely expanded with the development of the immune checkpoint inhibitors (ICIs)...
November 2018: Asia-Pacific Journal of Clinical Oncology
Abhishek Tripathi, Elizabeth R Plimack
PURPOSE OF REVIEW: Until recently, effective treatment options for patients with advanced urothelial carcinoma were limited to platinum-based chemotherapy. In the post-platinum setting and for patients ineligible for cisplatin, minimally effective second-line chemotherapy was used and outcomes were poor. The approval of immune checkpoint inhibitors has significantly changed the treatment landscape of urothelial carcinoma. Here, we review current data demonstrating their efficacy in advanced disease and ongoing trials investigating novel combination strategies...
November 7, 2018: Current Urology Reports
J Bedke, V Stühler, T Todenhöfer, A Stenzl
Immune checkpoint inhibitors (ICI) have significantly improved the systemic therapy of metastatic disease in genitourinary malignancies. With the European Medicines Agency (EMA) approval of the antibodies nivolumab and pembrolizumab directed against programmed cell death 1 (PD-1) as well as the PD-L1 antibody atezolizumab, three agents are available for the treatment of metastatic urothelial carcinoma and renal cell carcinoma. This article describes the underlying mode of action of PD-1/PD-L1 blockade and other ICIs to activate the immune system for effective tumor rejection...
November 2018: Der Urologe. Ausg. A
Jun Lu, Roberto J Firpi-Morell, Long H Dang, Jinping Lai, Xiuli Liu
The programmed death 1 (PD-1), programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) immune checkpoints are negative regulators of T-cell immune function. Inhibition of these targets by antibodies (PD-1 blocking therapy) has been explored to treat solid malignancies such as melanoma, non-small cell lung cancer and other cancers. PD-1 blocking therapy is known to cause gastrointestinal tract adverse events in some patients and some of the adverse events are thought to be immune-mediated...
October 2018: Gastroenterology Research
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"