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Pembrolizumab and bladder

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https://www.readbyqxmd.com/read/29784744/the-changing-treatment-landscape-for-metastatic-urothelial-carcinoma
#1
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/29745928/cancer-immunotherapy-and-the-pd-1-pd-l1-checkpoint-pathway
#2
Jonathan Barclay, Joanne Creswell, Juan León
Long-term survival for patients with advanced bladder cancer is precarious, with a 5-year survival of just 5% in metastatic cases. Normally, the binding of PD-L1 to PD-1 alters the immune activity by modulating it to inhibit autoimmune diseases or chronic inflammation. However, some cancers use this route to block the immune response of the patient and continue growing. The new immunotherapy against bladder cancer aims to block the ability of tumor cells to resist patient' immune response by acting on the checkpoints of immune cells...
May 2018: Archivos Españoles de Urología
https://www.readbyqxmd.com/read/29726785/medication-use-evaluation-of-programmed-death-1-inhibitors-in-a-veteran-population
#3
Vivianne Nguyen, Mostaqul Huq
Objectives To evaluate the safety and efficacy of programmed death-1 immune checkpoint inhibitors in a clinical practice setting. Methods Chart reviews were conducted on a total of 21 Veterans with advanced or metastatic cancers treated with programmed death-1 checkpoint inhibitors between 1 January 2015 and 31 July 2017. Among them, 16 patients were treated with nivolumab, including 12 with non-small cell lung cancer, 2 with melanoma, and 2 with bladder cancer. Pembrolizumab was used in 5 patients, including 4 with melanoma and 1 with head and neck cancer...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29576265/cost-effectiveness-of-pembrolizumab-in-second-line-advanced-bladder-cancer
#4
Michal Sarfaty, Peter S Hall, Kelvin K W Chan, Kiran Virik, Moshe Leshno, Noa Gordon, Assaf Moore, Victoria Neiman, Eli Rosenbaum, Daniel A Goldstein
BACKGROUND: Immune-modulating drugs have recently been introduced to the second-line setting of advanced bladder cancer. Pembrolizumab increases overall survival and is associated with less toxicity compared with chemotherapy in this setting based on the Keynote 045 study. The high cost of immunotherapy necessitates an assessment of its value by considering both efficacy and cost. OBJECTIVE: To estimate the cost-effectiveness of pembrolizumab for the second-line treatment of advanced bladder cancer from the perspective of payers in multiple countries...
March 22, 2018: European Urology
https://www.readbyqxmd.com/read/29562804/a-network-meta-analysis-of-the-pd-l-1-inhibitors-in-the-salvage-treatment-of-urothelial-bladder-cancer
#5
Elie El Rassy, Ziad Bakouny, Fouad Aoun, Fadi G Haddad, Ghassan Sleilaty, Tarek Assi, Joseph Kattan
AIM: To determine which of the approved immune checkpoint inhibitors is the optimal treatment in metastatic urothelial bladder cancer. METHODS & MATERIALS: Only the pivotal Phase III trials of second-line metastatic urothelial bladder cancer were included in this network meta-analysis. RESULTS: This NMA included three pooled trials (NCT00315237, NCT02256436 and NCT02302807) of 1125 participants. Pembrolizumab was the only treatment with positive effect on overall survival compared with the best supportive care...
March 22, 2018: Immunotherapy
https://www.readbyqxmd.com/read/29284318/pembrolizumab-for-the-treatment-of-bladder-cancer
#6
Nora Sundahl, Sylvie Rottey, Daan De Maeseneer, Piet Ost
Until recently, patients with locally advanced or metastatic urothelial carcinoma after progression on cisplatin-containing chemotherapy had limited systemic treatment options with no significant survival benefit and poor tolerability. Advances in the field of immunotherapy with the introduction of checkpoint inhibitors have led to paradigm shifts in the treatment of various malignancies. Areas covered: The current review will summarize the clinical evidence of checkpoint inhibitors in bladder cancer, with a focus on pembrolizumab...
February 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29239187/-immunotherapy-for-bladder-cancer
#7
T Büchler
Urothelial carcinoma is the most common urological malignancy. Nonspecific immunotherapy using the Bacillus Calmette-Guerin vaccine has long been the mainstay for the treatment of high-risk superficial bladder carcinoma in an adjuvant setting after transurethral endoscopic resection. In metastatic disease, cisplatin-based chemotherapy remains the main therapeutic modality. In Europe, the standard second-line chemotherapy for patients with cisplatin-refractory tumours is vinflunine. Other systemic treatments with a lower level of evidence include paclitaxel and docetaxel...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29157296/biomarkers-for-immunotherapy-in-bladder-cancer-a-moving-target
#8
REVIEW
David H Aggen, Charles G Drake
Treatment options for metastatic urothelial carcinoma (mUC) remained relative unchanged over the last 30 years with combination chemotherapy as the mainstay of treatment. Within the last year the landscape for mUC has seismically shifted following the approval of five therapies targeting the programmed cell death protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis. Notably, the anti-PD-1 antibody pembrolizumab demonstrated improved OS relative to chemotherapy in a randomized phase III study for second line treatment of mUC; this level 1 evidence led to approval from the U...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29146734/humanized-mice-in-studying-efficacy-and-mechanisms-of-pd-1-targeted-cancer-immunotherapy
#9
Minan Wang, Li-Chin Yao, Mingshan Cheng, Danying Cai, Jan Martinek, Chong-Xian Pan, Wei Shi, Ai-Hong Ma, Ralph W De Vere White, Susan Airhart, Edison T Liu, Jacques Banchereau, Michael A Brehm, Dale L Greiner, Leonard D Shultz, Karolina Palucka, James G Keck
Establishment of an in vivo small animal model of human tumor and human immune system interaction would enable preclinical investigations into the mechanisms underlying cancer immunotherapy. To this end, nonobese diabetic (NOD).Cg- Prkdcscid IL2rgtm1Wjl /Sz (null; NSG) mice were transplanted with human (h)CD34+ hematopoietic progenitor and stem cells, which leads to the development of human hematopoietic and immune systems [humanized NSG (HuNSG)]. HuNSG mice received human leukocyte antigen partially matched tumor implants from patient-derived xenografts [PDX; non-small cell lung cancer (NSCLC), sarcoma, bladder cancer, and triple-negative breast cancer (TNBC)] or from a TNBC cell line-derived xenograft (CDX)...
March 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29069302/mechanistic-overview-of-immune-checkpoints-to-support-the-rational-design-of-their-combinations-in-cancer-immunotherapy
#10
A Rotte, J Y Jin, V Lemaire
Checkpoint receptor blockers, known to act by blocking the pathways that inhibit immune cell activation and stimulate immune responses against tumor cells, have been immensely successful in the treatment of cancer. Among several checkpoint receptors of immune cells, cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), T-cell immunoglobulin and ITIM domain (TIGIT), T-cell immunoglobulin-3 (TIM-3) and lymphocyte activation gene 3 (LAG-3) are the most commonly targeted checkpoints for cancer immunotherapy...
January 1, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28982752/urothelial-carcinoma-of-the-bladder-and-the-rise-of-immunotherapy
#11
REVIEW
David D Chism
With the advent of platinum-based chemotherapy, survival rates for metastatic urothelial carcinoma have plateaued, giving way to the modern immunotherapy paradigm. Although immunotherapy as an effective treatment dates back to the live, attenuated bacillus Calmette-Guérin vaccine, the recent impact of immune checkpoint inhibitors targeting programmed death/programmed death-ligand 1 (PD-1/PD-L1) coupled with the promise of both anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies and indoleamine-2, 3-dioxygenase-1 (IDO-1) inhibitors have provided a resurgence...
October 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28982750/bladder-cancer-version-5-2017-nccn-clinical-practice-guidelines-in-oncology
#12
Philippe E Spiess, Neeraj Agarwal, Rick Bangs, Stephen A Boorjian, Mark K Buyyounouski, Peter E Clark, Tracy M Downs, Jason A Efstathiou, Thomas W Flaig, Terence Friedlander, Richard E Greenberg, Khurshid A Guru, Noah Hahn, Harry W Herr, Christopher Hoimes, Brant A Inman, Masahito Jimbo, A Karim Kader, Subodh M Lele, Joshua J Meeks, Jeff Michalski, Jeffrey S Montgomery, Lance C Pagliaro, Sumanta K Pal, Anthony Patterson, Elizabeth R Plimack, Kamal S Pohar, Michael P Porter, Mark A Preston, Wade J Sexton, Arlene O Siefker-Radtke, Guru Sonpavde, Jonathan Tward, Geoffrey Wile, Mary A Dwyer, Lisa A Gurski
This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on systemic therapy for muscle-invasive urothelial bladder cancer, as substantial revisions were made in the 2017 updates, such as new recommendations for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. The complete version of the NCCN Guidelines for Bladder Cancer addresses additional aspects of the management of bladder cancer, including non-muscle-invasive urothelial bladder cancer and nonurothelial histologies, as well as staging, evaluation, and follow-up...
October 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28883282/development-of-immune-checkpoint-inhibitors
#13
Shigehisa Kitano
Immune checkpoint inhibitors are the most striking innovation in the clinical development of immunotherapy. Monoclonal antibodies (mAbs) restore and augment the antitumor immune activities of cytotoxic T cells by mainly blocking immune checkpoint molecules on T cells or their ligands on antigen-presenting and tumor cells. Based on preclinical data, many clinical trials have demonstrated the acceptable safety profiles and efficacies of mAb in various cancers. The A first-in-class approved immune checkpoint inhibitor is ipilimumab, which is a fully humanized mAb that blocks the immunosuppressive signal by cytotoxic T-lymphocyte antigen 4...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28877075/microsatellite-instability-a-predictive-biomarker-for-cancer-immunotherapy
#14
Liisa Chang, Minna Chang, Hanna M Chang, Fuju Chang
Immunotherapy has shown promising results in various types of cancers. Checkpoint inhibitor drugs developed for cancer immunotherapy have been approved by the US Food and Drug Administration (FDA) for patients with advanced melanoma, non-small cell lung cancer, renal cell carcinoma, bladder cancers, and refractory Hodgkin lymphoma. In the latest announcement, the FDA has granted accelerated approval to pembrolizumab for pediatric and adult patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient solid tumors...
February 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28864844/checkpoint-inhibitors-the-new-treatment-paradigm-for-urothelial-bladder-cancer
#15
REVIEW
Heather Katz, Emnet Wassie, Mohamed Alsharedi
Bladder cancer is the most common malignancy involving the genitourinary system (Siegel et al. in CA Cancer J Clin, 66:7-30, 2016). In the USA, it is the fifth most common cancer and approximately 79,000 new cases will be diagnosed in 2017 (Siegel et al. in CA Cancer J Clin, 66:7-30, 2016). The mortality from bladder cancer is approximately 17,000 deaths each year (Siegel et al. in CA Cancer J Clin, 66:7-30, 2016). The incidence rate for bladder cancer is higher in men compared to women. Risk factors are predominantly related to tobacco smoking, although infection with Schistosoma haematobium is another risk factor in selected populations (Antoni et al...
September 1, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28749907/immunotherapy-in-urothelial-cancer-part-1-t-cell-checkpoint-inhibition-in-advanced-or-metastatic-disease
#16
REVIEW
Steven S Yu, Tanya B Dorff, Leslie K Ballas, Sarmad Sadeghi, Eila C Skinner, David I Quinn
Cancer of the urothelium is the sixth most common cancer in the United States and is seen predominantly in men. Most cases of this disease present as non-muscle-invasive bladder cancer (NMIBC), with cancer recurrence or progression to muscle-invasive cancer in more than 50% of patients after initial therapy. NMIBC is an immune-responsive disease, as indicated by the use of intravesical bacillus Calmette-Guérin as treatment for more than 3 decades. More recently, immunotherapy has seen much progress in a variety of cancers, including advanced and metastatic bladder cancer, in which historical 5-year survival rates are approximately 15%...
June 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/28493171/immunotherapy-in-urothelial-cancer-recent-results-and-future-perspectives
#17
REVIEW
Matthew S Farina, Kevin T Lundgren, Joaquim Bellmunt
Cytotoxic chemotherapy has been the only systemic treatment of locally advanced and metastatic urothelial carcinoma for decades. Long-term survival remains stagnant around 12-14 months for patients with advanced disease who have progressed on or recurred after receiving first-line platinum-based chemotherapy. Improving clinical outcomes for patients with urothelial carcinoma in all disease settings requires the development of novel treatments, especially for patients who failed on first-line chemotherapy. Since the discovery of intravesical Bacillus-Calmette Guerin (BCG) in the 1970s for non-muscle invasive disease, there have not been any major breakthrough drugs that exploit the immune-sensitivity of bladder cancer until recently...
July 2017: Drugs
https://www.readbyqxmd.com/read/28288994/immunotherapy-beats-chemo-for-bladder-cancer
#18
(no author information available yet)
Patients with advanced urothelial carcinoma live 3 months longer, on average, when given pembrolizumab as a second-line treatment instead of chemotherapy. The finding is based on data from the first phase III trial to test an immunotherapeutic in these patients, which could lead to another label indication for the PD-1 inhibitor.
May 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28266514/bladder-cancer-pembrolizumab-is-superior-to-chemotherapy
#19
Peter Sidaway
No abstract text is available yet for this article.
May 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28214651/a-review-on-the-evolution-of-pd-1-pd-l1-immunotherapy-for-bladder-cancer-the-future-is-now
#20
REVIEW
Joaquin Bellmunt, Thomas Powles, Nicholas J Vogelzang
The treatment of bladder cancer has evolved over time to encompass not only the traditional modalities of chemotherapy and surgery, but has been particularly impacted by the use of immunotherapy. The first immunotherapy was the live, attenuated bacterial Bacillus Calmette-Guérin vaccine, which has been the standard of care non-muscle-invasive bladder cancer since 1990. Modern immunotherapy has focused on inhibitors of checkpoint proteins, which are molecules that impede immune function, thereby allowing tumor cells to grow and proliferate unregulated...
March 2017: Cancer Treatment Reviews
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