Immunotherapy for Bladder Cancer

Immunotherapy is the use of medicines to help a person’s own immune system recognize and destroy cancer cells. Immunotherapy is sometimes used to treat bladder cancer.

Intravesical BCG

BCG is a type of bacteria related to the one that causes tuberculosis. While it doesn’t usually cause a person to get sick, it can help trigger an immune response. BCG can be put right into the bladder as a liquid. This activates immune system cells in the bladder, which then attack bladder cancer cells.

For more details on this treatment, see the section on intravesical therapy.

Immune checkpoint inhibitors

An important part of the immune system is its ability to keep itself from attacking normal cells in the body. To do this, it uses “checkpoints” – molecules on immune cells that need to be turned on (or off) to start an immune response. Cancer cells sometimes use these checkpoints to keep from being attacked by the immune system. But newer drugs that target these checkpoints hold a lot of promise as cancer treatments. At this time, these drugs are used to treat bladder cancers that have spread to other parts of the body (stage IV).

Atezolizumab (Tecentriq^®), durvalumab (Imfinzi^®), and avelumab (Bavencio^®) are drugs that target PD-L1, a protein on cells (including some cancer cells) that helps keep the immune system from attacking them. By blocking PD-L1, these drugs boost the immune system's response against the cancer cells. This can shrink some tumors or slow their growth.

Nivolumab (Opdivo^®) and pembrolizumab (Keytruda^®) target PD-1, another protein that normally helps keep the immune system in check. Blocking PD-1 can allow the immune system to attack the cancer cells.

Any of these checkpoint inhibitors can be used in people with advanced bladder cancer that starts growing again after chemotherapy. Atezolizumab and pembrolizumab can also be used in people who can't get the chemo drug cisplatin (due to things like hearing loss, kidney failure, or heart failure).

For certain bladder cancers that are not growing into the muscle wall of the bladder, not getting smaller with intravesical BCG, and not being treated with a cystectomy, pembrolizumab may be recommended.

These drugs are given as intravenous (IV) infusions, usually every 2 or 3 weeks.

Possible side effects

Common side effects of these drugs include:

• Fatigue
• Nausea
• Loss of appetite
• Fever
• Urinary tract infections (UTIs)
• Rash
• Diarrhea
• Constipation

Less often, more serious side effects can occur. These drugs work by basically taking the brakes off the body’s immune system. Sometimes the immune system starts attacking other parts of the body, which can cause serious or even life-threatening problems in the lungs, intestines, liver, hormone-making glands, or other organs.

It’s very important to report any new side effects to your health care team right away. If serious side effects do occur, treatment may need to be stopped and you may get high doses of steroids to suppress your immune system.

Monoclonal antibodies

Antibodies are proteins made by your immune system to help fight infections. Man-made versions, called monoclonal antibodies, can be designed to attack a specific target, such as a protein on the surface of bladder cancer cells. This means these treatments attack cancers cells, but ignore normal cells that don't have the target. This reduces damage to normal, healthy cells.

Enfortumab vedotin-ejfv (Padcev)

Bladder cancer cells usually have the Nectin-4 protein on their surface. Enfortumab vedotin-ejfv is an anti-Nectin-4 antibody attached to a chemo drug, called monomethyl auristatin E (MMAE). The antibody part of enfortumab acts like a homing signal, bringing the chemo drug to the bladder cancer cells with Nectin-4 on them. The chemo enters the cancer cells and kills them.

Enfortumab may be used to treat people with advanced bladder cancer who have already been treated with platinum chemotherapy (such as cisplatin) and immunotherapy (specifically, a PD-1 or PD-L1 inhibitor).

Enfortumab is infused into a vein (IV), once a week for 3 weeks with one week off.

Common side effects include fatigue, peripheral neuropathy (a type of nerve damage), nausea, taste changes, decreased appetite, diarrhea, rash, hair loss, dry eye, dry skin, itching, and high blood sugar levels.