New Hope for Treating Advanced Endometrial Cancer
- A combination of multiple therapies, including an immunotherapy (Infinzi), a PARP inhibitor (Lynparza), and chemotherapy showed promise in treating some patients with advanced endometrial cancer.
- Endometrial cancer starts in the inner lining of the uterus, called the endometrium. Previously, there had not been many good treatment options for women with advanced disease.
- Both Imfinzi plus Lynparza and Imfinzi alone significantly improved progression-free survival (how long a patient lives without their disease worsening) in advanced endometrial cancer when added to chemotherapy.
A new study demonstrated that combining an immunotherapy drug called durvalumab (brand name: Infinzi) with a PARP inhibitor olaparib (brand name: Lynparza) showed a greater clinical benefit compared to the other treatment plans studied.Read More
Combining treatments, whether it's immunotherapy and chemotherapy or two immunotherapies, may be an option for certain patients with endometrial cancer.
Combining therapies can help increase efficacy, may help with cases where a patient becomes resistant to other drugs, and may help treat difficult cases of endometrial cancer that have advanced to the metastatic stage (spread to distant parts of the body).
In a long overdue development, a combination of durvalumab (Infinzi), olaparib (Lynparza), and chemotherapy, delayed disease progression for patients with advanced disease.
How Does Infinzi Work?
Infinzi is a type of immunotherapy called human monoclonal antibody. It is a small molecule that binds to certain proteins on the surface of cancer cells. These include PD-1, PD-L1, and CD80 proteins that help cancer cells evade destruction by a patient's native immune system.
More specifically, PD-1 and CD80 are proteins expressed on several immune cells. These proteins can interact with PD-L1, a conjugate protein expressed by tumor cells, essentially rendering tumors invisible to and safe from the immune system.
Had this interaction been prevented, the errant tumors cell could have been eliminated by the immune system. Infinzi accomplishes just that by binding to PD-L1 and preventing it from interacting with PD-1 and CD80 proteins.
How Does Lynparza Work?
Lynparza belongs to a class of medication called poly-ADP ribose polymerase (PARP) inhibitors. These medications work by preventing cancer cells from repairing their damaged DNA, which eventually leads to their death.
What Does the Data Show?
Imfinzi plus Lynparza and Imfinzi alone both significantly improved progression-free survival in advanced endometrial cancer when added to chemotherapy. For patients with advanced endometrial cancer, or disease that has come back, they have historically had few treatment options that effectively target their cancer.
This trial shows that this immunotherapy-PARP inhibitor combo can fill that critical gap.
The investigators involved in the DUO-E trial intend to present a comprehensive analysis of their findings at an upcoming medical meeting and engage in discussions regarding the results with regulatory health authorities.
About the Study
The study enrolled 699 patients in 253 locations across 22 countries including the US, South America, Europe, and Asia. All patients had newly diagnosed or recurrent advanced epithelial endometrial carcinoma (stages III or IV).
It was a double-blind, randomized, multicentre, placebo-controlled trial. That means that the study was really well designed.
“The reports of the positive results is exciting and really shows promise for the treatment of advanced stage and metastatic endometrial cancer, which is universally considered difficult to treat. There has been a lot of momentum lately in the treatment of this group of patients and I look forward to seeing the results.” – says Dr Gerber.
What is Endometrial Cancer?
Among women worldwide, endometrial cancer ranks as the sixth most prevalent cancer, with over 417,000 reported cases and more than 97,000 fatalities in the year 2020.
Diagnoses are expected to rise by almost 40% by 2024 and long-term outcomes in first line treatment remain poor, highlighting the urgent need for innovative and improved therapeutic approaches.
Endometrial cancer starts in the inner lining of the uterus, called the endometrium, according to the American Cancer Society.
The uterus is the pear-shaped organ where the fetus grows and develops during pregnancy. During a woman's menstrual cycle, the hormone estrogen causes endometrium to thicken and, if there is no pregnancy, the hormone progesterone causes the endometrial lining to shed and become the menstrual flow.
Risk factors for endometrial cancer, according to the National Cancer Institute, include:
- Taking estrogen-only hormone replacement therapy (HRT) after menopause
- Taking tamoxifen (hormone therapy drug known by the brand name Soltamox) to prevent or treat breast cancer
- Having metabolic syndrome, a group of conditions that raise the risk of heart disease, stroke, and diabetes
- Having type 2 diabetes
- Exposure of endometrial tissue to estrogen made by the body, sometimes a result of never having given birth
- Menstruating at an early age (Menstruation typically begins between 10 and 16)
- Starting menopause at a later age (Menopause typically begins between 45 and 55)
- Having polycystic ovarian syndrome.
- Having a family history of endometrial cancer in a first-degree relative (mother, sister, or daughter).
- Having certain genetic conditions, such as Lynch syndrome.
- Having endometrial hyperplasia.
Symptoms of endometrial cancer may appear similar to those of other conditions, so it's important to bring any concerning symptoms or changes to your doctor.
Signs of endometrial cancer include:
- Vaginal bleeding or discharge that's not related to menstruation
- Vaginal bleeding after menopause
- Difficult or painful urination
- Pain during sex
- Pain in the pelvic area
How is Endometrial Cancer Diagnosed?
Women might be familiar with a certain test they get from their primary doctor or gynecologist, called a Pap test, or Pap smear. This procedure, in which a small brush is used to gently scrape cells from the surface of the cervix, only checks for cervical cancer. So other procedures are needed to help diagnose endometrial cancer.
This may include:
- Endometrial biopsy: With this procedure, a thin and flexible tube is inserted through the cervix and into the uterus and used to gently scape tissue from the endometrium. A specialist looks at the tissue under a microscope for cancer cells.
- Dilatation and curettage: With this procedure, a tool is used to open the vagina and a small spoon-shaped instrument is inserted into the uterus to gently remove tissue to remove samples of tissue from the inner lining of the uterus.
- Hysteroscopy: With this procedure, a thin tube with a light and camera is inserted through the vagina and cervix and into the uterus to look for abnormal areas. This procedure may also gently remove tissue to look for cancer.
Doctors may also perform a physical exam or pelvic exam, as well as a trans-vaginal ultrasound, in which an ultrasound probe is inserted into the vagina to examine the examine the vagina, uterus, fallopian tubes, and bladder for tumors.
Stages of Endometrial Cancer
Endometrial cancer can be divided into the following stages:
- Stage 1: Found in the uterus only.
- Stage 2: Has not spread beyond the uterus, but cancer has been found in the connective tissue of the cervix.
- Stage 3: Spread beyond the uterus and cervix, such as to the outer layer of the uterus, the fallopian tubes, the ovaries, ligaments or vagina. Stage 3C means the cancer has spread to the lymph nodes in the pelvis or near the aorta artery.
- Stage 4: Spread beyond the pelvis, to areas such as to the bladder, bowel wall, abdomen, or groin lymph nodes.
Treatment for Endometrial Cancer
How doctors choose to treat your endometrial cancer can depend on a few factors, including whether it has spread to other areas beyond the endometrium, what the cancer cells look like, and whether the cancer cells are affected by the hormone progesterone.
Low-risk endometrial cancer tend not to spread, and high-risk cancer has a tendency to spread.
Based on the risk and stage of the cancer, standard treatment options include:
- Surgery to remove cancer, which may include removing the entire uterus (total hysterectomy)
- Radiation therapy
- Hormone therapy
- Targeted therapy, which includes immunotherapies like the ones used in the studies above
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?
- Would I benefit from a PARP inhibitor?
- What do you feel is the best initial treatment for me?
- Are there ways to manage the side effects of the treatment I receive?