The first bladder cancer drug targeting a cancer-driving gene mutation has been used relatively little despite its clear efficacy in a clinical trial, suggests a report published as a research letter by Nimgaonkar et al in JAMA Oncology. Researchers analyzed a large, nationwide database of cancer cases and found that between 2019 and 2021, in a sample of nearly 800 patients with bladder cancer potentially eligible for treatment with erdafitinib, fewer than half had a record of being tested for the relevant gene mutation. Of those who were tested and found to have the mutation, fewer than half received the treatment.

“The uptake of this drug was unexpectedly low, which suggests that there are significant barriers to its use, including obstacles that prevent people from getting tested for the erdafitinib-susceptible gene mutation,” said first study author Vivek Nimgaonkar, BA, BS, a Perelman School of Medicine student and graduate associate with the Penn Center for Precision Medicine. “Our research has implications for patients, who start later lines of therapy after receiving a platinum-based chemotherapy, and it’s important that patients receive the necessary testing to have the full range of therapeutic options available to ensure the best possible chance for good outcomes.”

Role of FGFR

About 20% of advanced urothelial carcinomas are driven by mutations that cause growth-related receptors called FGFRs (fibroblast growth factor receptors) to be overactive. Erdafitinib works as an inhibitor of FGFR activity. Based on results from a phase II clinical trial, which showed much higher rates of tumor response to the drug than is normally seen in patients with advanced urothelial cancer, erdafitinib was provisionally approved—subject to further studies—by the U.S. Food and Drug Administration (FDA) in early 2019. It is meant to be used in patients who have susceptible FGFR mutations and are no longer responding to standard chemotherapy.

“Genetic testing needs to be more widely available for patients to learn about and access, and education for treating physicians is a must so they can gain knowledge on the benefits and value in use for eligible patients,” said senior study Ronac Mamtani, MD, MSCE, an Assistant Professor of Medicine at the Hospital of the University of Pennsylvania.

Current Analysis of Use

The new analysis covered a total of 761 patients who were eligible for FGFR mutation testing from April 1, 2019, to September 1, 2021. Of the 761, only 343 (45.1%) had a record of FGFR testing. Of these, 71 (20.7%) had evidence of an FGFR mutation that would render their cancer susceptible to erdafitinib—but just 30 (42.3%) of those 71 patients actually received treatment with erdafitinib.

The results also showed that, among patients expected to harbor susceptible FGFR alterations, the effective uptake rate for erdafitinib in its first 6 months postapproval was far lower than the initial uptake rate for atezolizumab—which, in published trials, has had a lower response rate than erdafitinib.

The analysis indicated that the median survival time (about 9 months) for erdafitinib-treated patients was in line with results from the prior clinical trial.

Theories for Low Uptake Rates

The study was not designed to discover why the uptake of erdafitinib was so low. However, the researchers suggest that the drug’s high cost—over $20,000 per month—and potential side effects, including mouth sores and the loss of fingernails, may have accounted in part for the low rate of uptake even among patients whose tests showed susceptible FGFR mutations.

The low rate of FGFR testing, the researchers added, may have been due in part to the novelty of genetic testing for patients with bladder cancer. Moreover, tumor genetic testing in general has traditionally been done on biopsied tumor samples, which may often have been unavailable when patients became eligible for testing. Only about 22% of patients with FGFR testing in the study had the newer, blood-based liquid biopsy testing, which detects circulating tumor DNA and is much easier for patients but is not yet standard in this area of oncology.

“We see tremendous opportunity to increase the proportion of eligible patients who get FGFR mutation tests by encouraging more use of liquid biopsies,” said study coauthor Erica L. Carpenter, MBA, PhD, Research Assistant Professor of Medicine; member of the Institute for Translational Medicine and Therapeutics at the University of Pennsylvania; and Director of the Liquid Biopsy Laboratory at the University of Pennsylvania.

Disclosure: For full disclosures of the study authors, visit jamanetwork.com.