Immunotherapy for Cervical Cancer
Each year more than half a million women are diagnosed with cervical cancer. Almost all cases are caused by human papillomavirus (HPV), a common sexually transmitted infection that can now be prevented with a vaccine. Usually, an HPV infection is harmless, and the body’s immune system can successfully fight it off. Sometimes, however, the infection causes cellular changes in the cervix that lead to the development of cancer.
How is cervical cancer treated?
When detected early—usually through a routine screening test such as a Pap smear—cervical cancer can often be effectively treated. Traditionally, the three pillars of cervical cancer treatment have been surgery, radiation therapy and chemotherapy. Although chemo can be highly effective for treating advanced and recurrent cervical cancer, it has some limitations. Some drugs specifically target a certain cellular characteristic that is not present in every cervical cancer cell. Other drugs non-specifically target the DNA of rapidly growing cells, which are not always cancerous. As a result, the drugs may damage healthy cells and cause adverse side effects.
As the landscape of cancer care continues to evolve, the treatment options for cervical cancer are increasing. Over the last few decades, innovative cancer research has led to the development of immunotherapy, a new class of drugs that capitalize on the infection-fighting power of the body’s own immune system to target and destroy cancerous cells. Because cervical cancer is caused by an infection, it is particularly well suited for immunotherapy.
Recently, the U.S. Food and Drug Administration (FDA) approved some promising immunotherapies for cervical cancer:
An essential function of the body’s immune system is to recognize - and not attack - healthy cells. To do so, the immune system uses proteins found on the surface of certain infection-fighting white blood cells (T cells). Known as “checkpoints,” these proteins must be “turned on” to trigger an immune response. Some cervical cancer cells exploit the function of the checkpoints by keeping them turned off. As a result, the cancerous cells can slide by unscathed.
Immune checkpoint inhibitors are a class of drugs that target the immune checkpoints to treat cancer. One example is pembrolizumab (Keytruda®), which binds to a checkpoint known as PD-1. Normally, PD-1 serves as an “off switch” to keep the immune cells from attacking healthy cells. To do so, PD-1 attaches to PD-L1, a protein found on the surface of some healthy—and some cancerous—cells. Some cervical cancer cells have a large amount of PD-L1, which helps them masquerade as healthy cells and effectively blocks the body’s immune response against them.
Immunotherapies that prevent PD-1 and PD-L1 from attaching can effectively “release the brakes” on the checkpoints. This can keep the cancerous cells from hiding, bolster the immune response against them and possibly shrink a tumor or slow its growth.
Antibodies and Antibody Drug Conjugates (ADCs)
An antibody is a lab-created protein that has the potential to attach to certain cells and then trigger a response that can inhibit cellular growth. An antibody-drug conjugate is a new class of drug that uses such an antibody and attaches it to a very active anticancer drug. Its goal is to deposit a potent drug that may otherwise be too toxic to be given by itself inside of cancerous cells. This antibody binds to proteins found on the surface of cancer cells to target those specific cancerous cells.
Bevacizumab (Avastin®) is a monoclonal antibody that is approved to treat cervical cancer. Healthy cells produce a protein known as vascular endothelial growth factor (VEGF), which stimulates the formation of new blood vessels. By binding to VEGF, bevacizumab can prevent it from binding to its signaling receptor, VEGF receptor 2, and inhibit the growth of new blood vessels that feed a tumor. As such, bevacizumab can “starve” the tumor of the blood it needs to grow and survive.
Tisotumab vedotin (Tivdak™) is an antibody drug conjugate that is attached to monomethyl auristatin E (MMAE), a microtubule inhibitor that acts as a form of chemotherapy. It is currently the only FDA-approved antibody-drug conjugate in cervical cancer. This “chemoimmunotherapy” medication targets a protein known as tissue factor (TF), which is found in healthy cells and helps with blood clotting. Some cancerous cells also have TF on their surface, and an excessive amount can facilitate tumor growth and spread. Tisotumab vedotin-tftv works by binding to the TF receptors on a cancerous cell, then pushing the chemotherapy drug directly into the cell. This chemotherapy drug can then kill the cancer cell from the inside.
Benefits of immunotherapy for cervical cancer
Immunotherapy is unique in that it offers the possibility of long-term cervical cancer control. First, it “trains” the body’s immune system to “remember” cancerous cells, then the resulting “immunomemory” can provide lasting protection against a recurrence, long after the treatment ends.
When might a doctor recommend immunotherapy as a treatment option for cervical cancer?
Before suggesting pembrolizumab for cervical cancer treatment, a physician will order a lab test to determine whether the cancerous cells test positive for PD-L1. If sufficient PD-L1 is detected, pembrolizumab may be used:
- On its own to treat recurrent cervical cancer
- On its own to treat cervical cancer that spreads during or after chemotherapy
- In combination with chemotherapy to treat cervical cancer that did not respond to traditional treatments
- In combination with chemotherapy to treat cervical cancer that spread to distant areas of the body
A physician may suggest the use of tisotumab vedotin or chemotherapy and bevacizumab for an adult woman with persistent, recurrent or metastatic cervical cancer.
Immunotherapy vs. chemotherapy for cervical cancer
Cancer immunotherapy drugs work by harnessing and enhancing the natural powers of the body’s immune system, enabling it to better recognize, target and destroy cancerous cells. Chemotherapy drugs work by attacking rapidly dividing cells throughout the body, effectively targeting fast-growing tumors—along with some healthy cells, such as those that line the mouth and intestines and those that cause the hair to grow.
Side effects of immunotherapy for cervical cancer
Compared to chemotherapy, immunotherapy is usually easier on the body. The main reason is that chemo drugs indiscriminately target rapidly dividing cells. Therefore, the treatment often damages healthy cells, which can lead to disruptive side effects such as nausea, mouth sores, hair loss and impaired concentration (“chemo brain”).
With that said, immunotherapy can also cause side effects, most of which are a result of unintended inflammation to different organs in the body.
- Skin rash
- Loss of appetite
- Diarrhea or constipation
- Joint and muscle pain
- Hormonal imbalances
- Inflammation of various organs: colitis, pneumonitis, hepatitis, pancreatitis, thyroiditis, hypophysitis
Because many patients who receive immunotherapy for cervical cancer have previously received chemotherapy, they are often well prepared to cope with mild side effects, most of which are related to inflammation. Still, it is important to discuss any side effects with a physician, who may pause the immunotherapy or prescribe an immunosuppressant to reduce the associated inflammation.
Effectiveness of immunotherapy for cervical cancer
Many researchers and clinicians believe the future of immunotherapy holds great promise for improving long-term outcomes and quality of life for patients with cervical cancer. Numerous immunotherapy trials are underway, and scientists continue to learn more every day. Due to its proven effectiveness, the combination of pembrolizumab and chemotherapy with or without bevacizumab has become the standard of care for patients with PD-L1-positive cervical cancer.
More Studies Underway
Researchers continue to evaluate and develop new immunotherapies and other antibody-drug conjugates as well as other several promising options are now being tested in clinical trials. One example involves the manipulation of tumor-infiltrating lymphocytes, which are immune cells that are found inside a tumor but in an insufficient quantity to destroy the cancer. Scientists are currently exploring ways to harvest these lymphocytes, growing them in a lab to induce their rapid reproduction and reintroduce the cancer-fighting cells to the tumor in a much larger quantity.
How Moffitt Cancer Center approaches immunotherapy for cervical cancer
The renowned research team at Moffitt is continually exploring new ways to harness the power of the body’s immune system to more effectively fight cancer. Currently, we are evaluating several promising new treatment options for cervical cancer in our robust portfolio of clinical trials. Due in part to our commitment to improving cancer care through research, we have earned the prestigious Comprehensive Cancer Center designation from the National Cancer Institute.
If you would like to learn more about immunotherapy for cervical cancer, you can talk with our gynecologic oncologist in the Gynecologic Oncology program. We do not require referrals. Request an appointment by calling 1-888-663-3488 or submitting a new patient registration form online.