How Does Immunotherapy Work for Gynecologic Cancers?

Immunotherapy is a category of cancer treatment that uses the body’s immune system to recognize, target, control, and eliminate certain types of cancer cells. Because the immune system is so precise, using it to fight cancer is unlike other treatments out there. 

Immunotherapy drugs help the immune system:

• Attack cancer cells, leaving healthy cells intact
• Continuously adapt to changes in cancer, re-evaluate the situation, and launch a new attack
• “Remember” the cancer cells, target and kill them if cancer recurs
• Boost immune cells to maximize their cancer-fighting ability

Immunotherapies are not available for all types of cancer just yet. There has been a tremendous clinical research effort to find out how they can be used for various types of cancer, including some gynecologic cancers.

Immunotherapy is often used in combination with surgery, chemotherapy, radiation, and/or targeted therapies for maximum effectiveness. There are a few categories of immunotherapy approved. Each one is being studied extensively for how they can be developed further to help even more cancer patients.

• Monoclonal antibodies and checkpoint inhibitors - Made in a lab, these antibodies slow or stop the growth of abnormal proteins in cancer cells. When used as an immune checkpoint inhibitor, cancer cells aren’t able to “trick” the body into thinking they’re healthy cells so they can keep growing.  This is the most commonly approved type of immunotherapy at this time. 
• T-cell therapy (CAR T-cell therapy) - The patient’s own T-cells are removed from the blood. Next, a lab-created receptor is added to the T-cells, which are put back in the body. The receptors are able to identify cancer cells and destroy them. 
• Cancer vaccines - These vaccines come in two categories: cancer prevention and cancer treatment. Several prevention vaccines are currently available. Treatment vaccines are still mostly in the research phase to see how they can use the body’s immune system to identify and destroy specific types of cancer cells. 
• Oncolytic virus therapy - Currently, with limited approval but under extensive research, viruses are changed in a laboratory and injected into a patient to destroy cancer cells.           

How is immunotherapy used to treat gynecologic cancers?

Gynecologic cancers result from the rapid growth and spread of abnormal cells in a woman’s reproductive organs (uterus, cervix, ovaries, vagina, vulva). Each type of gynecological cancer has a different set of treatments that are considered part of the regular course of therapy. Immunotherapy is now becoming more common in the treatment process for ovarian cancer, cervical cancer, and uterine (endometrial) cancer.

Immunotherapies Approved for Cervical Cancer

The Food and Drug Administration (FDA) has approved a few immunotherapies for women who have developed cervical cancer, both in the monoclonal antibody/checkpoint inhibitor category:

• Targeted antibodies have been approved for advanced cervical cancers. 
• Bevacizumab (Avastin), a monoclonal antibody, is a special category of cancer treatment called anti-angiogenic therapy. It targets the VEGF/VEGFR pathway and inhibits tumor blood vessel growth. It is used in combination with chemotherapy.
• Tisotumab vedotin (Tivdak) is an antibody-drug conjugate targeting tissue factors (TF).
• Pembrolizumab (Keytruda) is a monoclonal antibody that blocks the PD-1 protein on cervical cancer cells. This keeps the cancer cells from disguising themselves as healthy cells. When this happens the patient’s T cells can do their job of attacking the cancer cells.
• Immunomodulators are checkpoint inhibitors approved for advanced cases of cervical cancer. 

Cancer Prevention Vaccines Are Available for Cervical Cancer

Because most cervical cancer cases are related to HPV, the logical thing to do is prevent HPV. HPV vaccines are extremely successful in preventing new cases of HPV-related cancers of the cervix, vagina, vulva, and anus. While this isn’t a cancer treatment, the benefits of prevention are well-established and may even be helpful for those who already have an HPV infection.

The Cervarix vaccine is used to prevent infection by the two most common cervical cancers; Gardasil prevents infection by four types of HPV. The Gardasil-9 vaccine prevents infection by seven types of HPV and two types of HPV that cause genital warts.

Immunotherapy Treatment for Ovarian Cancer

Most cases of ovarian cancer are advanced by the time they’re diagnosed because symptoms (bloating, constipation and gas) are often mistaken for other health issues. Because of this, it can be hard to successfully treat ovarian cancer, and quite often, it will return. 

Most ovarian cancer patients respond to chemotherapy, but resistance to chemo can develop, causing periods of remission and then relapse. Patients with recurrent ovarian cancer or ovarian cancer that is Stage 2 or higher may have immunotherapy included at some point in their treatment.

Immunotherapies for Ovarian Cancer 

There are some approved immunotherapies for ovarian cancer, with a few more nearly ready for approval:

• Targeted antibody-drug Bevacizumab (Avastin), an anti-angiogenic monoclonal antibody, targets the VEGF/VEGFR pathway and stops tumor blood vessel growth. This basically starves the cancer cells of the blood supply they need to grow. This is approved for newly diagnosed or relapsed ovarian cancer patients and can be used in combination with chemotherapy.
• Two immunomodulators have been fast-tracked for approval (meaning that the research is being reviewed sooner because of promising early results) for advanced ovarian cancer: Dostarlimab (Jemperli) for platinum-resistant ovarian cancer and Pembrolizumab (Keytruda). Both are checkpoint inhibitors that target the PD-1/PD-L1 pathway.

Immunotherapies That Treat Endometrial (Uterine) Cancer

Endometrial cancers develop in the cells that line the inside of the upper uterus. It’s easy to treat if detected early. Typical treatments for endometrial or uterine cancer include surgery, radiation, hormone therapy, targeted therapies, and chemotherapy, with available immunotherapy options.

In addition to the two treatments below, other immunotherapies are being tested in clinical trials. These two immunomodulators -- both are checkpoint inhibitors -- have received FDA approval for endometrial cancer:

• Dostarlimab (Jemperli), which targets the PD-1 pathway, is approved for patients with recurrent or advanced endometrial cancer.
• Pembrolizumab (Keytruda) targets the PD-1/PD-L1 pathway and is approved for advanced cancers, and, in combination with lenvatinib, it’s approved for recurrent endometrial cancers.

Immunotherapy Side Effects

Side effects of immunotherapies can be severe but are manageable in most cases if treated early. Stimulating the immune system with immunotherapy drugs can cause a range of side effects, from minor inflammation and flu-like symptoms to potentially life-threatening conditions. This is usually caused when the immunotherapy drug causes the body to target healthy cells in the body in addition to the cancer cells. 

The severity depends on how healthy the patient was before treatment, the type of gynecologic cancer, how advanced it is, and the type of therapy used. Common side effects can include rash, diarrhea or nausea, fatigue, body aches, headaches, and changes in blood pressure. Widespread inflammation is a rarer side effect. 

The Latest Gynecologic Cancer Treatments Available in Portland and Vancouver

The newest gynecologic cancer treatment methods are available at Compass Oncology. And we continue to research new and better options by participating in clinical trials. The gynecologic oncologists at Compass Oncology will provide the information, counseling, and treatment plan for each patient based on a number of factors. Because of this, every patient’s treatment plan is unique. If you or a loved one has a gynecologic cancer diagnosis, request an appointment with one of our gynecologic cancer specialists.