For Advanced Bladder Cancer, The Drug Balversa Is Now FDA Approved– A Promising Therapy For People With Specific Mutations

Balversa works by targeting genetic mutations called FGFR3 and FGFR2.

FGFR stands for fibroblast growth factor receptors. These are proteins that give cells their orders to grow and divide. When there is a mutation in the FGFR genes, cells are directed to make these proteins which helps bladder cancer to grow.

Balversa, made by Johnson & Johnson, is the first and only targeted therapy for patients with locally advanced or metastatic urothelial carcinoma and susceptible fibroblast growth factor receptor (FGFR) genetic alterations. These are present in about 20 percent of cases.

Balversa received accelerated approval in 2019 and breakthrough therapy designation in 2018 from the FDA. Balversa is not recommended for patients who are eligible for and have not received prior PD-1 or PD-L1 inhibitor therapy.

The THOR trial

The phase 3 THOR trial was presented at the 2023 American Society of Clinical Oncology (ASCO), the largest cancer conference in the world.

The trial enrolled 266 adults with advanced/metastatic urothelial cancer harboring specific FGFR alterations. It’s known that around 20% of metastatic urothelial carcinomas have FGFR mutations account.

All patients had experienced disease progression after two or fewer prior lines of therapy, including chemotherapy and immunotherapy. Patients’ median age was 67 years and they were randomly assigned to receive Balversa or the investigator’s choice of chemotherapy.

The study compared Balversa to chemotherapy or pembrolizumab, which are other medicines for used to treat bladder cancers. The study found that Balversa helped people live longer and stop the cancer from growing.

In the study, people who took Balversa lived for 12.1 months on average, while people who took chemotherapy or pembrolizumab lived for 7.8 months on average. This means that Balversa reduced the risk of death by 36%.

“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.”

The study also showed that Balversa stopped the cancer from growing for 5.6 months on average — nearly double the amount of time compared to chemotherapy or pembrolizumab.

The study also found that 45.6% of people who took Balversa had their tumors shrink, while only 11.5 percent of people who took chemotherapy or pembrolizumab had their tumors shrink.

“These results demonstrate improved responses and survival outcomes for patients receiving erdafitinib (Balversa) compared to standard-of-care chemotherapy, confirming the benefit for these patients,” said Dr. Arlene Siefker-Radtke, who was a senior investigator on the trial. “This highlights the significance of a targeted therapy option for patients with FGFR-altered urothelial cancer and is the first biomarker-targeted therapy for this disease.”

Key details about Balversa

Balversa represents a promising advancement for the treatment of metastatic bladder cancer with FGFR3 or FGFR2 alterations, as it offers a personalized and effective option for patients who have limited choices and poor outcomes with standard therapies.

However, Balversa also has some common side effects.

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

However, Dr. Richards 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%).

Overall, Balversa represents a promising advancement for the treatment of metastatic bladder cancer with FGFR3 or FGFR2 alterations. But it is not a cure and it may not work for everyone.

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

Is Bladder Cancer Common?

According to the National Cancer Institute, bladder cancer ranks as the sixth most prevalent cancer type in the United States overall, while it is the fourth most common among men.

Like any other cancer, bladder cancer can spread beyond the organ where it started. It can reach nearby lymph nodes, or other parts of your body.

You may have been diagnosed with an advanced bladder cancer to start. Or you might have discovered that your cancer had spread after being treated for an early-stage cancer. Either way, your treatment direction will change.

In 2023, there were 82,290 new cases of bladder cancer and about 16,710 deaths from the disease In the United States, according to the American Cancer Society.

Of these cases, around 35% are classified as locally advanced, indicating that the cancer has spread to the surrounding tissues of the bladder, or metastatic, indicating that it has spread to other parts of the body.

Bladder cancer primarily affects individuals over the age of 55. Unfortunately, the five-year survival rate for these advanced cases is only 5%.

Historically, chemotherapy using cisplatin has been the standard treatment for advanced bladder cancers. Although cisplatin is highly effective, it carries significant toxicity risks, particularly for the kidneys.

Urologic oncologist Dr. Mark Tyson explains the treatment options for later-stage bladder cancer. 

Considering that bladder cancer primarily affects an older population with potential kidney impairment, cisplatin is not always a suitable option. Consequently, approximately 50% of cisplatin-ineligible patients have been treated with less effective drugs. As a result, Balversa helps fill a pressing need for treatments that can prolong survival in these patients.

FGFR Mutations

Erdafitinib (Balversa) blocks FGFR to stop cancer cells from growing.

But what are FGFR?

Fibroblast growth factor receptors — or FGFRs — are proteins that give cells their orders to grow and divide. Mutations to the FGFR genes direct cells to make these proteins, which then help bladder cancer cells grow. Up to 20% of people with advanced bladder cancer that’s returned or is resistant to treatment have one of these mutations.

If you have advanced bladder cancer, a mutation in the FGFR3 or FGFR2 gene, or your cancer kept growing after treatment with platinum-based chemotherapy, then you might be able to get this drug.

“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 in a previous conversation.

He adds that he often steers patients who have the FGFR3 mutation to a combination treatment approach. “That includes an FGFR3-targeted drug, along with immunotherapy or another combination that addresses FGFR3, to make sure that we’ve given that patient the best chance to respond,” he said.

Dr. Yohann Loriot of the Gustave Roussy, University Paris-Saclay in Villejuif, France and one of the authors of the THOR study added, “The data are thus extremely important because they clearly show that the strategy to inhibit FGFR2/3 gene alterations affects the management of patients with metastatic urothelial cancer.”

Genetic Testing

How do you know if you qualify for treatment with a targeted drug like Balversa? The answer lies in genetic testing.

“Genetic testing, in my opinion, is one of the most important things that we can counsel patients about,” Dr. Balar said.

Genetic tests identify changes called mutations in your genes. These are mistakes in your genetic code that happen when cells divide, or when you’re exposed to certain things in the environment.

Research has linked several mutations to bladder cancer. Some of these mutations, like FGFR, affect the cancer cells’ ability to grow, divide, and survive.

When to Get Tested

“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.

To find these gene mutations, your doctor will need a sample of tissue from your tumor. Usually your doctor will take that sample during a biopsy. You may also need to give a blood sample for the analysis.

Dr. Balar recommends testing as soon after you’re diagnosed as possible. Genetic test results can take up to 10 weeks, and you don’t want them to hold up your treatment.

“For some patients, I advocate for early testing to have that information available early on. So that when and if it’s needed, that information is readily available to make a treatment decision,” Dr. Balar said.

Potential Side Effects of Balversa

The negative effects of immunotherapy can be quite severe, so it’s important to inform your physician as soon as you experience any abnormal symptoms. Those who are taking more than one immunotherapy drug, referred to as combination therapy, are at an increased risk of experiencing side effects.

Common Immunotherapy side effects include:

• Mouth sores
• Feeling tired
• Change in kidney function
• Diarrhea
• Dry mouth
• Change in liver function
• Low salt (sodium) levels
• Decreased appetite
• Change in sense of taste
• Low red blood cells (anemia)
• Hair loss
• Redness, swelling, peeling or tenderness, mainly on the hands or feet ("hand-foot syndrome")
• Constipation
• Stomach (abdominal) pain
• Nausea
• Muscle pain

You should call your doctor right away if you experience any of the following side effects:

• Eye problems
  • Dry or inflamed eyes
  • Blurred vision
  • Loss of vision
  • Any other vision changes
• Nail or skin changes
  • Nails separating from the nail bed
  • Nail pain, bleeding, or nail breaking
  • Nails that have changed color or texture
  • Infected skin around the nails
  • Dry skin or cracks in the skin
  • Itchy skin rash

Questions to Ask Your Doctor:

Here are some questions you may consider asking your doctor to help understand your situation and whether Balversa may make sense for you:

• Am I a good candidate for Balversa?
• What do you feel is the best initial treatment for me?
• Would it make sense for me to receive Balversa sooner rather than later?
• Do you expect me to have any negative side effects from receiving Balversa?
• Can you help me understand how much I may have to pay out-of-pocket in order to have Balversa?
• Are resources available to help me pay the bill?

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