A study has demonstrated that patients with advanced bladder cancers whose tumors have a mutated FGFR3 gene respond to immunotherapy treatment in a manner that is similar to patients without that mutation, a discovery that runs counter to previous assumptions.
This research, led by scientists at the University of North Carolina Lineberger Comprehensive Cancer Center, has important implications for patients who have not been offered immunotherapy because of their genetic profiles.
The findings are published in the British Journal of Cancer.
“Despite prior work suggesting that FGFR3-mutated bladder cancers should not be treated with immunotherapy, our study demonstrates the opposite, so we believe that immunotherapy should be offered without hesitation,” said corresponding author UNC Lineberger’s William Y. Kim, Rush S. Dickson Distinguished Professor of Medicine and professor of genetics.
There have been several recent significant treatment advances for bladder cancer. In 2019, the FDA approved a drug, erdafitinib (Balversa), that targets FGFR3 and prolongs survival. Additionally, immune checkpoint blockade drugs, commonly known as immunotherapies, have recently been approved for advanced bladder cancer. Prior to this decade, treatment was primarily limited to systemic, platinum-based chemotherapy.
“Clinical trials have shown that bladder cancers with FGFR3 mutations have fewer immune cells, primarily T cells, than cancers without the mutation. Because tumors with low levels of immune cells tend to respond poorly to immune checkpoint blockades, it has been hypothesized that those patients would have low response rates to immunotherapy,” said co-first author UNC Lineberger’s Tracy Rose, assistant professor at the UNC School of Medicine.
To test the hypothesis, UNC Lineberger researchers designed a study to compare tumor tissue samples and clinical trials data from 17 patients with FGFR3-mutated bladder cancer to 86 patients whose tumors did not have the mutation.
The investigators found that patients with FGFR3 mutations responded to immunotherapy equally as well as those without the mutations. At a cellular level, they also found equivalent diversities of T cell receptors and a similar balance of immune suppression and immune activation signals in tumors with and without FGFR3 mutations. This equivalency, or balance, indicates a similar chance of benefiting from immunotherapy.
The researchers hope to establish a clinical trial to test whether patients with FGFR3 alterations benefit more from erdafitinib or immunotherapy.
“Our study does not rule out the possibility that erdafitinib will synergize with immunotherapy,” said William Weir, co-first author and an MD-PhD student at UNC-Chapel Hill. “If anything, the fact that FGFR3-altered patients benefit from immunotherapy argues that this may be a reasonable approach.”
