The FDA announced in April 2019 that it had approved erdafitinib (Balversa), the first personalized therapy targeting a genetic alteration for treatment of advanced bladder cancer.
“We’re in an era of more personalized or precision medicine, and the ability to target cancer treatment to a patient’s specific genetic mutation or biomarker is becoming the standard,” Richard Pazdur, MD, acting director of the FDA Oncology Center of Excellence, said at the time of the approval.
There are other firsts when it comes to erdafitinib. It is the first fibroblast growth factor receptor 3 (FGFR3) inhibitor and first oral agent approved for the treatment of bladder cancer, according to Arlene Siefker-Radtke, MD, professor of genitourinary medical oncology at The University of Texas MD Anderson Cancer Center, Houston.
Determining if advanced bladder cancer patients are candidates for the FGFR3 inhibitor involves genetically testing bladder cancer tumor tissue for the presence of an FGFR mutation, according to Yair Lotan, MD, professor and chief of urologic oncology at UT Southwestern Medical Center in Dallas.
“For bladder cancer patients who have either metastatic disease or patients with advanced disease who might become metastatic, there is value in knowing whether or not they have FGFR mutations, so one would know whether or not erdafitinib is a treatment option available to them,” Dr. Lotan said.
Tumor genetic testing with a tumor specimen is different than the clinical genetic testing for germline heritable mutations, according to Elizabeth Plimack, MD, MS, chief of genitourinary medical oncology at Fox Chase Cancer Center, Philadelphia.
“Fortunately, with bladder cancer we often have banked tissue from a patient’s biopsy or surgery,” Dr. Plimack said. “But it’s really the medical oncologist that’s going to order the test and choose which specimen to send because the test result is most relevant at the point of metastases. A patient with localized disease may never be metastatic or be a candidate, in which case they do not require testing. For a patient with metastatic disease who then quickly recurs, based on currently available data, they should go through prior treatment before erdafitinib makes sense. Erdafitinib is not usually a first-line treatment.”
Urologists often see bladder cancer patients whose disease has progressed despite standard treatment that might involve surgery and chemotherapy. Some metastatic patients have had the option of immunotherapy, but if that was ineffective, treatment options were limited, according to urologist Badrinath Konety, MD, MBA, professor of urology at the University of Minnesota, Minneapolis.
Now, with erdafitinib, which binds to FGFR1, FGFR2, FGFR3, and FGFR4, many of these patients have a new option for second-line therapy.
“The other option of course is immunotherapy,” Dr. Konety said. “The advantage of erdafitinib is that it’s oral, it seems to be well-tolerated, and it’s based on a receptor that is more widely expressed as opposed to PD-1 or PD-L1, which are not as widely expressed. The FGFR mutation is one of the most common mutations you’ll find in bladder cancer, so more patients may be eligible for this treatment.”
The urologist’s role in erdafitinib treatment could soon expand.
“There are some clinical trials that are looking at FGFR inhibitors in patients with Bacillus Calmette-Guerin (BCG)-unresponsive disease,” Dr. Lotan said. “It wouldn’t yet be standard of care to test for FGFR in a patient without advanced disease, but that doesn’t mean that in the near future—the next few years—it won’t become something of value.”
Biomarkers, in general, have many potential uses in bladder cancer treatment. In fact, the International Consultation of Urologic Diseases has devoted 2020 to molecular markers and their roles in bladder, prostate, and other urologic cancers, according to Dr. Lotan, who is editor for the ICUD’s bladder section.