Immunotherapy for Patients with Advanced Urothelial Cancer: Current Evidence and Future Perspectives

Abstract

In recent years, immunotherapy has produced encouraging results in a rapidly increasing number of solid tumors. The responsiveness of bladder cancer to immunotherapy was first established in nonmuscle invasive disease in 1976 with intravesical instillations of bacillus Calmette-Guérin (BCG). Very recently immune checkpoint inhibitors demonstrated good activity and significant efficacy in metastatic disease. In particular the best results were obtained with programmed death-ligand-1 (PD-L1) and programmed death-1 (PD-1) inhibitors, but many other immune checkpoint inhibitors, including anti-cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) antibodies, are currently under investigation in several trials. Simultaneously other therapeutic strategies which recruit an adaptive immune response against tumoral antigens or employ externally manipulated tumor infiltrating lymphocytes might change the natural history of bladder cancer in the near future. This review describes the rationale for the use of immunotherapy in bladder cancer and discusses recent and ongoing clinical trials with checkpoint inhibitors and other novel immunotherapy agents.

MTHFD2 is a potential oncogene for its strong association with poor prognosis and high level of immune infiltrates in urothelial carcinomas of bladder

“…PD1/PD-L1 antibodies, therefore, improved antitumor immunity. PD-L1 inhibitors, Atezolizumab and Durvalumab, were both approved by FDA for the treatment of patients with inoperable or metastatic UCB progressing on platinum-based treatment with positive PD-L1 [ 39 ]. A PD1 inhibitor, Pembrolizumab, has been approved in the first-line treatment of UCB patients ineligible for cisplatin with tumor PD-L1 positive [ 40 ].…”

“…A PD1 inhibitor, Pembrolizumab, has been approved in the first-line treatment of UCB patients ineligible for cisplatin with tumor PD-L1 positive [ 40 ]. These immune checkpoint inhibitors were exhibited to have significant efficacy and bring obvious survival benefits to patients with metastatic UCB [ 39 ].…”

Overall survival, costs, and healthcare resource use by line of therapy in Medicare patients with newly diagnosed metastatic urothelial carcinoma

“…Although it is not known why about half of the Medicare patients with UC remain untreated with chemotherapy, we have highlighted that they are likely to be older, sicker, and have worse performance status. As these patients may be untreated because of a reduced capacity for tolerating chemotherapy, they may be candidates for potentially better tolerated immuno-oncology therapies 29 . Indeed, it will be interesting to note whether the proportion of untreated Medicare patients and the patterns of treatments in the real world evolve as immuno-oncology therapies become available and are integrated into the overall management of mUC.…”

Update on the Treatment of Metastatic Urothelial Carcinoma

“…In the first-line setting, 8% of patients had to discontinue Atezolizumab due to treatment-related toxicity. One notable difference is that 20.5% of patients receiving avelumab had a grade 1-2 infusion-related reaction [ 42 , 43 ]. The quality of life for patients improved on nivolumab and remained stable with treatment.…”