Checkpoint inhibitors in bladder cancer

14th Meeting of the EAU Section of Oncological Urology (ESOU) Checkpoint inhibitors in bladder cancer G. Thalmann, Berne (CH) Immunotherapy is not a new option in the treatment genitourinary (GU) cancers and has been traditionally an important component of cancer treatment in urology. 40 years ago Morales reported on the use of intravesical Bacillus Calmette-Guérin (BCG) in non-muscle invasive bladder cancer (NMIBC). The immune system plays an important active role in surveillance and elimination of cells undergoing malignant transformation. Cells that have undergone malignant transformation as a result of accruing genomic mutations present tumour associated neoantigens (TAAs) on their cell surface via major histocompatibility complex class I (MHC-I). This then allows the activation of the immune system to recognize the tumor as “non-self” and thus to target the tumor. This reaction is modulated among other factors by immune checkpoint inhibitors which block an overreaction and potential autoimmune response. The 3 most important are a cytotoxic Tlymphocyte associated protein 4 (CTLA-4), programmed cell death (PD)-1 and PD-ligand-1 (PDL1). Ipilimumab (anti-CTLA-4), nivolumab and pembrolizumab (anti-PD-1), and atezolizumab (anti-PD-L1) are monoclonal antibodies targeting their ligand and specifically block the inhibitory receptor-ligand interaction at the T-cell membrane thus activating the immune response, in this case against tumor cells. There is a multitude of clinical trials ongoing currently that are testing these and many other checkpoint inhibitors against many tumors, also against urothelial cancer. The immune checkpoint inhibitor nivolumab (anti-PD-1) was recently approved by the FDA for the management of patients with advanced RCC patients previously treated with anti-angiogenic therapy. The safety profile and tolerability was good. In addition it has shown some promise in chemotherapy-resistant advanced urothelial carcinoma (UC), while FDA just approved atezolizumab for platinum-treated advanced UC. Results of ongoing studies are coming in every day and there are many combinations of immune checkpoint inhibitors with chemotherapeutics, vaccines, targeted tyrosine kinase inhibitors and monoclonal antibodies, and others, currently being tested in clinical trials. There is much research going on to increase our knowledge of the physiologically relevant factors underlying antitumor immune responses which will hopefully improve outcome in patients. Another important research effort is on the identification and validation of appropriate molecular biomarkers in order to be able to target treatment more effectively.

Eur Urol Suppl 2017; 16(2):118