The Options When Immunotherapy Stops Working
- Keytruda (pembrolizumab) is now a key part of bladder cancer treatment, but for some patients, the drugs either stop working on their own or must be stopped due to side effects.
- Keytruda is often given for about a year after surgery to help lower the risk that bladder cancer returns, as long as side effects remain manageable.
- If the cancer returns, doctors move to the next “line of therapy,” which may include chemotherapy, other immunotherapies, newer targeted drugs, or combination treatments.
- Clinical trials are often an important option when standard treatments stop working, giving patients access to promising therapies still being studied.
“Patients are given treatment for at least a year, sometimes longer, as long as they tolerate it,” Dr. Piyush Agarwal, a urologic oncologist at the University of Chicago, tells SurvivorNet.
Read MoreHow Long Patients Typically Take Keytruda
Pembrolizumab is commonly used in bladder cancer as adjuvant therapy, meaning it is given after initial treatment, such as surgery, to reduce the risk that cancer will return. Patients usually receive the medication for about one year, though the exact duration can vary depending on how well the treatment is tolerated and how the disease responds.“Keytruda and any of these immune therapies are given for a year, maybe more than a year after surgery in an adjuvant setting,” Dr. Agarwal explains. “A lot of medical oncologists are unwilling to stop the drug because the fear is the tumor might come back.”
In many cases, patients continue therapy for as long as the medication is working and side effects remain manageable. However, doctors must carefully balance the benefits of continuing treatment with the possibility that side effects could worsen over time.
“Patient toxicity can build up over time,” Dr. Agarwal explains.
Treatment is sometimes stopped if the side effects become too difficult for the patient.
Why Immunotherapy May Stop Working
Immunotherapy does not work the same way for every patient. Some people experience long-lasting responses, while others may eventually see their cancer grow again. There are several reasons this can happen.
Cancer cells are constantly evolving. Over time, tumors may develop new ways to avoid the immune system, even after initially responding to treatment. In other cases, the immune system simply cannot maintain enough pressure on the cancer cells to keep them under control indefinitely.
And sometimes treatment must be stopped because the side effects, which can affect the GI system, skin, and endocrine system, become too severe.
“When patients get to the point where they can’t tolerate it, unfortunately that is when the drug has to come off,” Dr. Agarwal says.
Determining Next Steps
If bladder cancer returns after immunotherapy, oncologists will reassess the situation and consider several possible strategies.
The next treatment path may depend on:
- How aggressive the recurrence is
- What treatments the patient has already received
- The patient’s overall health
- How long the previous treatment worked
In some cases, doctors may try the same drug again, Dr. Agarwal says. They may also try treatments that were used earlier in the course of care.
“Sometimes they’re given chemotherapy that they’ve been given already as well,” Dr. Agarwal says.
Cancer care often involves moving through different “lines of therapy.” Each line represents a new treatment approach when the previous one stops working. However, recurrent bladder cancer can be difficult to treat.
“These are difficult problems to solve when the tumor recurs and we exhaust through all our lines of therapy,” Dr. Agarwal says.
Newer Treatments Expanding Options
Although recurrence can be challenging, the treatment landscape for bladder cancer has improved dramatically over the past two decades. Not long ago, chemotherapy was essentially the only treatment option available. Today, doctors have a much broader set of tools.
This toolkit includes:
- Chemotherapy
- Immunotherapy (checkpoint inhibitors)
- Antibody-drug conjugates
- Combination therapies
Antibody-drug conjugates are a newer type of cancer treatment that combine targeted therapy with chemotherapy. These drugs deliver cancer-killing agents directly to tumor cells while trying to spare healthy tissue.
Some of these newer medications are already approved, while others are still being studied in clinical trials.
“We’ve got chemo, immunotherapy, antibody drug conjugates, combinations of those things … so we have a lot more to offer our patients,” Dr. Agarwal says.
Clinical Trials: An Important Option
When standard treatments stop working, clinical trials may offer additional options.
Clinical trials test new therapies or new combinations of treatments that are not yet widely available. They are often the first option doctors consider when patients have exhausted existing treatments, Dr. Agarwal says.
Many of the therapies available today, including immunotherapy drugs like Keytruda, became possible because patients participated in earlier clinical studies. Those trials helped researchers understand how to harness the immune system to fight cancer.
Today’s clinical trials continue to explore new strategies, including:
- New immunotherapy drugs
- Combination therapies
- Personalized treatments targeting specific tumor characteristics
For some patients, clinical trials provide access to promising therapies years before they become widely available.
If you want to participate in a clinical trial, your first step should be to talk with your doctor. They can address many of your initial questions and help you determine if you are eligible.
Another crucial part of clinical trials is finding the right one for you.
SurvivorNet has a resource to help with this called the Clinical Trial Finder.
Questions To Ask Your Doctor
- How long will I need to stay on immunotherapy?
- What side effects should I monitor for?
- Are there any new treatments or combinations I can try?
- Should I consider enrolling in a clinical trial?
Learn more about SurvivorNet's rigorous medical review process.
