Mutation-targeted Bladder Cancer Drug Found Under-used

“said the study’s lead author Vivek Nimgaonkar, a Perelman School of Medicine student and doctoral student with the Penn Center for Precision Medicine.

Our research has implications for patients who begin later courses of treatment after receiving platinum-based chemotherapy and it is important that patients receive the necessary tests to have the full range of therapeutic options available to ensure the best possible chance of good results.. “

The co-senior authors of the study were Ronac Mamtani, MD, and Erica Carpenter, MBA, PhD, who are both assistant professors of hematology / oncology at Penn. Dr. Carpenter is also head of the Liquid Biopsy Laboratory.

According to the American Cancer Society, approximately 81,000 Americans are diagnosed with bladder cancer each year – approximately 70 percent of them in men – and approximately 17,000 people die from the disease each year.

The five-year survival is about 77 percent, and bladder tumors are considered highly treatable when caught in the early stages. Later stages are much less treatable. Standard treatments include surgery, radiation, chemotherapy and immunotherapy.

The vast majority of bladder cancers occur from so-called urothelial cells that line the bladder and ureters and are called “urothelial carcinoma“About 20 percent of advanced urothelial carcinomas are driven by mutations that make growth-related receptors called FGFR (Fibroblast Growth Factor Receptors) overactive.

Erdafitinib acts as an inhibitor of FGFR activity. Based on promising results from a Phase 2 clinical trial, which showed a much higher frequency of tumor response to the drug than is normally seen in patients with advanced urothelial cancer, the drug was provisionally approved – subject to further study – by the US Food and Drug Administration ( FDA) in early 2019.

It is intended for use in patients who have sensitive FGFR mutations and who no longer respond to standard chemotherapy.

Genetic testing must be more widely available for patients to learn about and access, and training for treating physicians is a must so that they can gain knowledge of the benefits and value of use for qualified patients.“, said Dr. Mamtani.

The new assay included 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 percent) had a record of FGFR testing. Of these, 71 (20.7 percent) had evidence of an FGFR mutation that would make their cancer susceptible to erdafitinib. However, only 30 (42.3 percent) of these 71 patients received erdafitinib.

The results also showed that among patients expected to have sensitive FGFR changes, the effective uptake rate of erdafitinib, during the first six months after approval, was much lower than the initial uptake rate of the first immunotherapy for bladder cancer – as published in studies a lower response rate than erdafitinibs.

The analysis showed that the median survival time (approximately nine months) for erdafitinib-treated patients was in line with the results of the previous clinical trial.

The study was not designed to detect why erdafitinib uptake was so low. However, the researchers suggest that the drug’s high cost – over $ 20,000 per month – and potential side effects, including cold sores and loss of nails, may have partly explained the low uptake rate even among patients whose tests showed sensitive FGFR mutations.

The low frequency of FGFR testing, the researchers added, may be due in part to the novelty of genetic testing for bladder cancer. In addition, tumor genetic testing has generally been performed on biopsied tumor samples, which may often have been unavailable when patients were eligible for testing.

Only about 22 percent of the 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 not yet standard in this area of ​​oncology.

We see a huge opportunity to increase the proportion of qualified patients receiving FGFR mutation tests by encouraging more use of liquid biopsies“said Dr. Carpenter.

Source: Medindia

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