Stage 4 Bladder Cancer Treatment Advancements
- SurvivorNet experts agree that immunotherapy and targeted therapy are changing the game when it comes to treating stage four, or metastatic, bladder cancer.
- Immunotherapy works by boosting your body’s own immune response to help it stop the cancer.
- Targeted therapy focuses on the processes that help cancer cells grow; it’s a more precise way to treat cancer than chemotherapy.
If you aren’t familiar with these types of cancer treatment options, you may be wondering what they are and how they works. Here’s the scoop:
What is Immunotherapy?Read More
Dr. Arjun Balar, director of the genitourinary medical oncology program at NYU Langone’s Perlmutter Cancer Center, tells SurvivorNet that there are five different immunotherapy drugs that have been approved as second-line treatment in advanced bladder cancer: atezolizumab (brand name: Tecentriq), nivolumab (brand name: Opdivo), pembrolizumab (brand name: Keytruda), durvalumab (brand name: Imfinzi) and avelumab (brand name: Bavencio).
The approvals for these drugs are after platinum chemotherapy — as the second-line treatment of choice. But two of these drugs, atezolizumab and pembrolizumab, have been approved for first-line treatment, “meaning the very first treatment that a patient receives for advanced or metastatic bladder cancer.”
“In fact, there were randomized trials that looked at immunotherapy versus chemotherapy after platinum chemotherapy, and it showed that it actually improved survival,” Dr. Balar says. “Using immunotherapy as our first treatment of choice after platinum chemotherapy is now our standard of care.”
How is Immunotherapy Used to Treat Metastatic Bladder Cancer?
“The advent of immunotherapy, specifically checkpoint-based immunotherapy, has revolutionized how we think about and how we treat advanced and metastatic bladder,” Dr. Dan Theodorescu, urological oncologist and director of the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai, tells SurvivorNet. “Now patients that have metastatic bladder cancer have the option for chemotherapy, the option for immunotherapy and immunotherapy following a failure of chemotherapy — if that has taken place.”
Dr. Jay Shah, staff surgeon and associate professor of urology at Stanford University, tells SurvivorNet that one of the questions he gets from patients is, “I have bladder cancer, and I want immunotherapy. Can you give me immunotherapy?”
“I think it’s important for patients to realize that immunotherapy agents are not standard of care yet for bladder cancer,” he says. (The key word there is yet.) “They have been approved for us to try using them in patients who can’t get any of the standard-of-care options.” And that standard-of-care option at the moment is cisplatin-based chemotherapy.
Dr. Shah explains that if a patient has advanced, metastatic bladder cancer and can’t get cisplatin-based chemotherapy, “then we can try to use immunotherapy to try to prolong that patient’s life and try to control that cancer. The lure with immunotherapy is that it doesn’t work with most patients, but in those patients where it works, there are responses that are phenomenal.”
But, as Dr. Theodorescu explains, advancements have been made in using chemotherapy and immunotherapy together when treating bladder cancer.
“The really exciting things that are happening now is really the combinations of chemotherapy with immunotherapy, with the idea of making the tumors even more sensitive…after they’ve been damaged or roughed up by the chemotherapy,” he says, “which causes all sorts of release of all sorts of things from the dying tumor that kind of enhanced and immunized the patient against their own cancer.”
Targeted Therapy: How is it Used to Treat Metastatic Bladder Cancer?
Targeted therapy is a more precise way to treat cancer than chemotherapy; chemo attacks many types of quickly dividing cells, including some healthy cells. Targeted therapy focuses on the processes that help cancer cells grow.
In 2019, the U.S. Food and Drug Administration approved erdafitinib (brand name: Balversa) — the first targeted therapy for bladder cancer. 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.
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.
“FGFR3 appears to be particularly important in bladder cancer,” Dr. Balar says. 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 says.
Balversa blocks FGFR to stop cancer cells from growing. The FDA approved the treatment based on the results of a clinical trial. In that study, about one third of people who took Balversa responded to it. Those who responded survived for an average of 5 and a half months without their cancer growing.
Antibody Drug Conjugate
Other recently approved systemic treatments for bladder cancer include the antibody drug conjugate enfortumab vedotin. This medicine targets bladder cancer cells that express nectin-4.
Bladder Cancer Subtypes
Ongoing bladder cancer research, Dr. Theodorescu says, is trying to identify if intrinsic bladder cancer subtypes are driving the response to immunotherapy and/or chemotherapy.
For example, he says, doctors have recently identified a subtype of bladder cancer, the cells of which are predominant in the cancer and portend for better response to immunotherapy, but for a worse response to chemotherapy.
“So you can envision, if you had that knowledge in stratifying a patient based on that subtype inside the cancer, that they may end up going through immunotherapy for metastatic disease or advanced disease rather than chemotherapy,” Dr. Theodorescu says. “Conversely, they didn’t have that subtype, perhaps they should go to chemotherapy and then keep them in a therapy if they failed chemotherapy.”
“So we’re really, again, in the midst of another major advance with technologies that are able to identify or define the subtypes as we have reasonably done,” he says.
Contributing: Stephanie Watson