79,030 new cases estimated in 20172
90% of bladder cancers are urothelial carcinomas (UCs)3
Non–muscle-invasive bladder cancer (NMIBC) - 51%
Muscle-invasive bladder cancer (MIBC) - 41%
Metastatic urothelial carcinoma (mUC) - 4%
31% to 78% of patients with NMIBC will experience a recurrence or new occurrence of UC within 5 years4
The standard of care for MIBC comprises of cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy and bilateral pelvic lymph node dissection. High metastatic relapse rates still occur after radical cystectomy, which indicates that MIBC is a systemic disease at diagnosis in many patients5
The current 1L treatment recommendation is cisplatin-based combination chemotherapy, which places a toxic burden on patients. Only one immunotherapy agent is listed as category 1 for 2L mUC, according to NCCN guidelines6
TAKE A DEEPER LOOK at the unmet needs in the management of bladder cancer
HARNESSING THE IMMUNE SYSTEM
Bladder cancer has the fourth highest mutational burden among several tumor types.7
There is a need to enhance the body’s natural immune response in bladder cancer.10
Antigens introduced into the body resulting in an immune response, activating cytotoxic T cells or inducing antibody production13
Innate immune cell activation
Modulating immune response by targeting effector immune cells and immune cells, thus initiating a T-cell immune response14
Oncolytic viruses are injected into the tumor site, directly killing tumor cells and inducing a systemic immune response15,16
Immune checkpoint blockade
Targets key immune checkpoints to harness the innate immune response to eliminate tumor cells14
Immune checkpoint pathway inhibition, such as PD-L1 and CTLA-4, are the most widely studied systemic immune-based approach for the treatment of bladder cancer.17 Currently, there are five immunotherapy agents approved to treat metastatic UC.18 There are several ongoing clinical trials of checkpoint inhibitors in either monotherapy or combination therapy in earlier lines or stages of disease.19
NCCN=National Comprehensive Cancer Network; PD-L1=programmed cell death ligand-1; CTLA-4=cytotoxic T-lymphocyte-associated antigen-4.
NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
1. FDA approves new, targeted treatment for bladder cancer [press release]. Silver Spring, MD: Food and Drug Administration; May 18, 2016. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm501762.htm. Accessed June 26, 2017. 2. National Cancer Institute. Cancer stat facts: bladder cancer. https://seer.cancer.gov/statfacts/html/urinb.html. Accessed June 26, 2017. 3. Cancer.net. Bladder cancer. http://www.cancer.net/cancer-types/bladdercancer/. Accessed June 26, 2017. 4. Sylvester RJ, Van der meijden AP, Oosterlinck W, et al. Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol. 2006;49(3):466-475. 5. Funt SA, Rosenberg JE. Systemic, perioperative management of muscle-invasive bladder cancer and future horizons. Nat Rev Clin Oncol. 2017;14(4):221-234. 6. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Bladder Cancer v.5.2017. © National Comprehensive Cancer Network, Inc. 2017. All rights reserved. Accessed June 26, 2017. To view the most recent and complete version of the guidelines, go online to NCCN.org. 7. Rajasagi M, Shukla SA, Fritsch EF, et al. 2014. Systematic identification of personal tumor-specific neoantigens in chronic lymphocytic leukemia. Blood. 2014;124(3):453-462. 8. Choudhury NJ, Kiyotani K, Yap KL, et al. Low T-cell receptor diversity, high somatic mutation burden, and high neoantigen load as predictors of clinical outcome in muscle-invasive bladder cancer. Eur Urol Focus. 2016;2(4):445-452. 9. Kandoth C, McLellan MD, Vandin F, et al. Mutational landscape and significance across 12 major cancer types. Nature. 2013;502(7471): 333-339. 10. Intlekofer AM, Thompson CB. At the bench: preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy. J Leukoc Biol. 2013;94(1):25-39. 11. Muthigi A, George AK, Brancato SJ, Agarwal PK. Novel immunotherapeutic approaches to the treatment of urothelial carcinoma. Ther Adv Urol. 2016;8(3):203-214. 12. ClinicalTrials.gov. A phase 1/2 study of in situ vaccination with tremelimumab and IV durvalumab plus polyICLC in subjects with advanced, measurable, biopsy-accessible cancers. https://clinicaltrials.gov/ct2/show/NCT02643303. Accessed June 28, 2017. 13. National Cancer Institute. Cancer vaccines. https://www.cancer.gov /about-cancer/causes-prevention/vaccines-fact-sheet. Accessed July 18, 2017. 14. Farkona S, Diamandis EP, Blasutig IM. Cancer immunotherapy: the beginning of the end of cancer? BMC Med. 2016;14:73. 15. Hoos A. Development of immuno-oncology drugs—from CTLA4 to PD1 to the next generations. Nat Rev Drug Discov. 2016;15(4):235–247. 16. Chiocca EA, Rabkin SD. Oncolytic viruses and their application to cancer immunotherapy. Cancer Immunol Res. 2014;2(4):295–300. 17. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/results?cond=Bladder+Cancer&term=astrazeneca&cntry1=&state1=&Search=Search&recrs=a. Accessed June 28, 2017. 18. National Cancer Institute. FDA approves immunotherapy drugs for patients with bladder cancer. https://www.cancer.gov/newsevents /cancer-currents-blog/2017/approvals-fda-checkpoint-bladder. Accessed July 18, 2017. 19. AstraZeneca. Clinical trials appendix Q1 2017 results update. https://www.astrazeneca.com/content/dam/az/PDF/2017/QR1/Q1_2017_Results_Clinical_Trial_Appendix.pdf. Accessed July 7, 2017.