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Balversa’s FDA Approval Means a New, Practice-Changing Option for FGFR-Positive Bladder Cancer

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March 5, 2024

Clinical Relevance: Newly FDA-approved Balversa offers a targeted treatment option for patients with FGFR3-positive metastatic bladder cancer, demonstrating significant efficacy in progression-free and overall survival rates, and should be considered post platinum-containing chemotherapy or anti-PD-(L)1 therapy failures.


Oncologists now have a new option to consider in their decision-making process thanks to the full US Food and Drug Administration (FDA) approval of Balversa (erdafitinib) for patients with locally advanced or metastatic urothelial carcinoma.

The availability of Balversa marks a pivotal shift towards personalized treatment in bladder cancer. Its approval introduces Balversa as the first and only targeted therapy for individuals with FGFR3 genetic alterations, which are present in about 20% of cases.

“FGFR3 appears to be particularly important in bladder cancer,” Dr. Arjun Balar, director of the genitourinary medical oncology program at NYU Langone’s Perlmutter Cancer Center, told SurvivorNet.

Approval Overview

Initially granted accelerated approval in 2019 for its use in patients with FGFR3 or FGFR2 alterations who have progressed after platinum-containing chemotherapy, its indication has since been refined.

The latest approval restricts its use to FGFR3 alterations, following at least one line of prior therapy excluding those who are eligible for, but have not received, PD-1 or PD-L1 inhibitor therapy.

The drug stands out as a targeted therapy, specifically inhibiting FGFR kinases—enzymes crucial for the proliferation and survival of tumor cells in cancers with FGFR genetic alterations.

Balversa’s ability to target and inhibit FGFR3 and FGFR2 genetic alterations is pivotal in managing bladder cancer, as it directly interferes with the cancer cell growth and survival pathways.

The FDA’s approval reflects a deeper understanding of patient subgroups and the drug’s optimal positioning within the treatment paradigm.

Related: New Immunotherapy-Chemo Combo Approved for Metastatic Bladder Cancer Patients

THOR Study

FDA’s backing of Balversa was largely based on the results of the THOR study, a pivotal phase 3 clinical trial published in the New England Journal of Medicine, which assessed the efficacy of Balversa in patients with advanced or metastatic urothelial cancer with specific FGFR3 or FGFR2 genetic alterations.

This trial involved 266 patients, divided into two groups: 136 received Balversa, and 130 were treated with chemotherapy (docetaxel or vinflunine).

The primary endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS), objective response rate (ORR), and safety profiles​​​​.

At a median follow-up of 15.9 months:

  • Median OS for patients receiving Balversa was 12.1 months versus 7.8 months for those on chemotherapy, representing a 36% reduction in the risk of death.
  • Median PFS was 5.6 months for the Balversa group compared to 2.7 months for the chemotherapy group, indicating a 42% reduction in the risk of progression or death.
  • The ORR was significantly higher in the Balversa-treated group at 45.6% compared to 11.5% in the chemotherapy group​​​​.

“The patients on this trial had previously been treated with 1 or 2 treatments and their cancer had progressed. They also had to have a susceptible FGFR3/2 alteration which means that this therapy is more personalized and targeted,” American Urological Association member and Chief of Virginia Urology, Dr. Kyle A. Richards told SurvivorNet.

“Adding 4 and ½ months of survival is huge for patients with metastatic bladder cancer that had previously not responded well to other treatments,” he said.

Cohort 2 of the THOR study, comparing Balversa to the drug pembrolizumab, included 175 patients receiving Balversa and 176 patients receiving pembrolizumab.

This part of the study aimed to evaluate the efficacy and safety of Balversa in a specific patient population.

Key findings from this cohort:

  • Median OS was 10.9 months for patients receiving Balversa compared to 11.1 months for those receiving pembrolizumab. The hazard ratio (HR) was 1.18, indicating no significant difference in survival between the two treatments.
  • Median PFS for patients treated with Balversa was 4.4 months, while those treated with pembrolizumab had a median PFS of 2.7 months. This suggests that Balversa may delay disease progression more effectively than pembrolizumab.
  • ORR for Balversa was 40%, with 6.3% of patients achieving a complete response and 33.7% achieving a partial response. For pembrolizumab, the ORR was 21.6%, with 4.5% complete responses and 17% partial responses. This demonstrates a higher response rate to Balversa compared to pembrolizumab.
  • Median duration of response (DOR) was shorter for patients receiving Balversa (4.3 months) compared to those receiving pembrolizumab (14.4 months), indicating that while responses to Balversa were more frequent, they might not last as long as those to pembrolizumab.
  • The safety profiles of both treatments were consistent with previous studies. In the Balversa group, 13.3% of patients experienced serious treatment-related adverse events (TRAEs), and 15% discontinued treatment due to TRAEs. In contrast, the pembrolizumab group had a lower rate of serious TRAEs (10.4%) and discontinuations due to TRAEs (4.6%).

So, while Balversa showed a higher objective response rate and a slight improvement in progression-free survival compared to pembrolizumab in Cohort 2, the overall survival was similar between the two treatments.

Safety profile

Balversa had a higher discontinuation rate due to adverse events though its safety profile is generally characterized by manageable adverse effects, with guidelines for monitoring and dose adjustment to mitigate these risks.

“A side effect unique to the drug is elevated levels of phosphate in the blood which was noted in 80% of the patients,” Dr. Richards noted. “This needs to be monitored and is easily treated with a medication to bind the phosphate.”

Other commonly reported side effects include mouth sores, fatigue, diarrhea, nail disorders, and dry mouth. Importantly, the drug’s potential for serious eye problems necessitates vigilant monitoring, underscoring the importance of a multidisciplinary approach to patient care.

Balversa also requires the extra step of testing for FGFR3 or FGFR2 mutations using an FDA-approved companion diagnostic device before starting treatment.

“When I counsel a patient who’s undergoing their first treatment for advanced bladder cancer, I will often encourage them to undergo genetic testing. We may find a genetic marker that is present in their cancer that might help me direct them toward a specific clinical trial,” Dr. Balar said.

Dr.Balar pointed out that in the THOR trial, treatment related deaths were less common in the Balversa group (0.7%) compared to those treated with chemotherapy (5.4%).

However, Dr. Richard reiterated, the data strongly suggests that Balversa is not a cure and it may not work for everyone.

“Patients with bladder cancer should check with their urologists or medical oncologists to see if erdafitinib is a good choice for their situation,” he noted.

Watch: Exploring The Treatment Options For Metastatic Bladder Cancer