Findings from the international FORT-2 clinical trial showed that a combination treatment including immunotherapy is safe and tolerable in patients with locally advanced or metastatic bladder cancer. The results, published in JAMA Oncology , show the potential to broaden the number of patients with bladder cancer who could benefit from immunotherapy, an approach that harnesses a patient's own immune system to fight cancer. "The major problem with immunotherapy was it works great for some patients with bladder cancer, but the response rates never exceeded 25% with immunotherapy by itself, and our main focus is to try to understand the resistance to immunotherapy," said first author Randy Sweis, MD, Assistant Professor at the University of Chicago Medicine Comprehensive Cancer Center.
The tumor microenvironment (TME) plays a critical role in predicting response to immunotherapy. Tumors with a T-cell-inflamed microenvironment—which are characterized by infiltration of CD8 + T cells, chemokines, a group of protein that help in migration of immune cells, and an interferon signature—respond well to immunotherapies and are associated with improved survival. In urothelial bladder cancer, increased T cell infiltration has been correlated with longer patient survival.
In many cases, fibroblast growth factor receptor (FGFR) mutations are known to be drivers of bladder cancer development and progression. "In 2016, we published studies showing that the tumors with FGFR3 mutations have.