Immunotherapy in Advanced Endometrial Cancer
- Immunotherapy is a personalized treatment method that uses the body’s immune system to target cancer cells while sparing much of the healthy surrounding cells.
- Combining the immunotherapy drug, dostarlimab with traditional chemotherapy can significantly improve survival rates and slow the spread of the disease for patients with advanced endometrial cancer.
- While immunotherapy is often less toxic than traditional therapies such as chemotherapy and radiation, it can have some side effects.
- Side effects can vary quite a bit — from shortness of breath to skin issues like rashes or blisters to headaches, fatigue, and weight loss. It’s important to keep your medical team informed of any side effects you are feeling as your treatment plan may need an adjustment.
In some cases, the treatment plan may need to be altered due to immunotherapy side effects, but in others, patients can work with their doctors to mitigate the side effects in other ways.
Read MoreThat’s not to say it doesn’t have any side effects. About a third of patients experience some kind of reaction to immunotherapy. While they can be severe, they usually are manageable.
What are the Side Effects?
Immunotherapy basically takes the brakes off of the immune system. While that’s good for fighting cancer, it can sometimes cause an autoimmune reaction. Autoimmune means that your immune system attacks your body’s own organs and tissues by mistake.
For this reason, doctors generally don’t recommend immunotherapy for patients who already have autoimmune conditions such as Lupus or rheumatoid arthritis.
These immune responses cause side effects that can literally occur “in any tissue of the body from the top of the head to the tip of the toes,” Dr. Crispins explains.
“About a third of patients will experience some sort of immune toxicity, which you can basically think about as when we reactivate the immune system or when we get the immune system to recognize the cancer, sometimes it kind of overreacts or it recognizes things we don’t want it to recognize,” she says.
Therefore, there is a wide range of side effects patients and physicians must be on the look out for when immunotherapy is being given for treatment.
Side effects may present in the following areas:
- Intestines: diarrhea, belly pain
- Lungs: shortness of breath, cough
- Hormone-producing glands: headaches, fatigue, weight loss, weakness, belly pain, nausea and vomiting
- Joints and muscles: pain, weakness
- Lungs: shortness of breath, cough
- Skin: rash, itchy skin, blisters
- Heart: low blood pressure, abnormal heartbeat
Some people have an allergic-like reaction to the infusion. Infusion reactions cause side effects like these:
- Fever
- Chills
- Rash
- Itching
- Dizziness
- Wheezing
- Trouble breathing
Although having any drug side effect is no fun, in this case they do have an upside, Dr. Crispins points out.
“Interestingly, there’s some data that suggests that people who have those kinds of side effects may be responding better to the treatment,” she notes.
Work closely with your doctor and report any adverse effects you’re experiencing.
Managing Side Effects
Chemotherapy side effects are common, but they usually go away once the drugs are out of your system.
Immunotherapy is less likely to cause side effects. But when it does, those side effects can be severe and require prompt treatment to manage.
“It’s also important to know that, unlike regular chemotherapy where once the treatment is done, you’re not going to have new side effects, these immunotherapy side effects can continue to occur even after the drug is stopped,” Crispins adds.
If you do have side effects, your doctor might stop your immunotherapy treatment.
“If a patient is on an immunotherapy drug and there is any kind of new symptom, they should report that to their doctor right away so that we can evaluate because the earlier we intervene, we can mitigate the severity of some of those side effects,” Crispins says.
“Just because someone has one of those side effects doesn’t mean that they necessarily have to stop treatment depending on the severity and our ability to manage it,” she adds.
What is Immunotherapy?
This brand new treatment approach to endometrial cancer taps into the body’s immune system to identify and eliminate cancerous cells.
Normally, white blood cells find and destroy abnormal cells, but cancer cells learn to hide from them so they can continue growing and spreading.
Immunotherapy drugs find the cancer cells in their hiding places by blocking proteins that shield them. Once the cancer cells are uncovered, the immune system can do its job properly.
Another advantage to immunotherapy: because these drugs zero in on cancer cells while leaving much of the surrounding healthy tissue alone, they tend to be less toxic compared to traditional chemotherapy or radiation therapy which bombard both cancerous and healthy cells.
Immunotherapy can also provide a longer-lasting response by training the immune system to recognize and remember cancer cells, potentially reducing the risk of the cancer coming back.
The approach can be life changing — and possibly even life saving — for many patients.
However, it does not yet work for all patients with endometrial cancer. Ongoing research into combination therapies using immunotherapy will make this treatment even more effective for more people in the future.
Treating Endometrial Cancer With Immunotherapy
When treating advanced endometrial cancer, the National Comprehensive Cancer Network (NCCN) advises using immunotherapy, specifically immune checkpoint inhibition (ICI), as a key part of the treatment plan.
At these later stages, the cancer has spread from the uterus to nearby tissues, lymph nodes, or more distant parts of the body. The recommended approach combines chemotherapy drugs — carboplatin and paclitaxel — with an immunotherapy drug, either pembrolizumab (Keytruda) or dostarlimab (Jemperli), both of which are forms of ICI.
Both pembrolizumab and dostarlimab belong to a class of drugs known as monoclonal antibodies, which are lab-made proteins that target the PD-1 receptor on immune T-cells. Cancer cells often use this receptor to escape detection by the immune system. By blocking PD-1, these drugs enable the immune system to recognize and attack the cancer more effectively.
The decision between using pembrolizumab or dostarlimab often hinges on the genetic characteristics of the tumor, particularly its mismatch repair (MMR) status.
MMR is a cellular mechanism that fixes mistakes called mutations in the DNA replication process. Tumors that are mismatch repair deficient (dMMR) accumulate numerous mutations, which can make them more noticeable to the immune system.
Dr. Michael Toboni, an assistant professor in the division of gynecologic oncology at the University of Alabama at Birmingham, emphasizes the importance of MMR status in selecting the appropriate treatment.
“dMMR and endometrial cancers are mismatch repair deficient, which essentially means that there is a defect in one of four main genes that we test all endometrial cancers for,” Dr. Toboni explains. “If you do have a defect in one of those genes, you could have Lynch syndrome, which is a common hereditary cause of endometrial cancer. MMR proficient is when you do not have a defect in one of those genes, which is the majority of endometrial cancers, approximately 70%.”
For tumors that have a functioning mismatch repair system, known as MMR proficient (pMMR), and thus don’t exhibit certain genetic defects, a different treatment approach may be needed.
In these cases, doctors often recommend using a combination of two drugs: lenvatinib and pembrolizumab.
Lenvatinib targets and interferes with specific proteins that are essential for the tumor’s growth, while pembrolizumab strengthens the immune system’s ability to attack the cancer cells. This choice of treatment is based on a range of factors, including other genetic characteristics of the tumor or how the patient has responded to previous treatments.
Lenvatinib and pembrolizumab are not traditional chemotherapy drugs. They belong to classes of medication known as targeted therapy and ICI, respectively. Working together, they not only inhibit the cancer’s growth but also boost the body’s immune defense, offering a well-rounded approach to managing some types of endometrial cancer.
To find out if a tumor is MMR deficient or proficient, doctors run specific genetic tests on a sample of the tumor tissue. These tests are typically done early in the diagnosis process, allowing your medical team to tailor your treatment plan based on the genetic makeup of your cancer.
By understanding your tumor’s MMR status, you and your doctor can make more informed decisions about which therapies, such as the combination of lenvatinib and pembrolizumab or other immunotherapy options, might be most effective for you.
The Benefits of Immunotherapy
Combining immunotherapy with regular chemotherapy is a powerful way to slow down the disease’s progression and help patients live longer.
This treatment approach is particularly effective for patients with a specific genetic marker known as Microsatellite Instability (MSI), but studies show that all patients receiving this combination therapy tend to see some benefits.
MSI is a genetic marker characterized by changes in the length of microsatellites (short, repeated sequences of DNA) due to errors in the DNA mismatch repair system. Essentially, tumors with high levels of MSI accumulate numerous mutations, making them more recognizable to the immune system.
Targeting this genetic marker allows immunotherapy to identify cancer cells more precisely, as these markers are unique to the cancerous cells.
This personalized approach boosts treatment effectiveness while lowering the risk of side effects, leading to improved outcomes for those patients with this specific genetic profile.
Dostarlimab is approved for metastatic and recurrent endometrial cancer for patients who have the previously mentioned genetic mutations — mismatch repair-deficiency (dMMR) or microsatellite instability-high (MSI-H).
However, new data from the RUBY trial , revealed that this new drug, plus regular chemotherapy (carboplatin/paclitaxel) can be very effective for the treatment of patients with primary advanced or recurrent endometrial cancer, regardless of their mismatch repair status.
- Patients on the dostarlimab/chemo combo saw a 31% improvement in overall survival compared with placebo/chemotherapy in patients
- Their average survival from the beginning of treatment was 44.6 months, compared to 28.2 months for patients who did not receive the combo.
- 61% of the patients identified as having the dMMR or MSI-H markers treated with dostarlimab plus chemotherapy had no cancer spread after two years compared to less than 16% for a similar group who received a placebo.
- Patients given the dostarlimab/chemo combo had fewer side effects and tolerated their treatment well.
“Patients had much better outcomes than if they were treated with chemotherapy alone. So completely, and it didn’t matter whether they were deficient in MR protein, it didn’t matter what their microsatellite stability status was — in all comers, there was improved outcome,” Crispins says.
Another trial adds encouraging results as well. The GYO18 trial investigated the combination of pembrolizumab with standard chemotherapy for treating advanced or recurrent endometrial cancer. It found that the time to the cancer returning was delayed significantly, making pembrolizumab a promising option for women facing limited choices in advanced endometrial cancer.
Questions to Ask Your Doctor
If you have been diagnosed with advanced endometrial cancer, here are some questions you may consider asking your doctor to help understand your situation:
- What is the stage of my endometrial cancer?
- Am I eligible for immunotherapy?
- What benefits can I expect?
- What side effects can I expect?
- Are there ways to manage the side effects of the treatment I receive?
- How long will my treatment take and how will you measure how well I am doing?
- What will my treatment cost?
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