Treating Advanced Endometrial Cancer
- Two studies showed promising results in combining immunotherapy with chemotherapy to treat advanced or recurrent endometrial cancer.
- The studies found that the combo treatment may help slow the progression of the disease and help patients live longer.
- Chemotherapy, paclitaxel (brand name Abraxane) and carboplatin, is the current standard of care for first-line treatment.
- Immunotherapy is currently only approved to treat endometrial cancer after chemo, as a second-line treatment.
- Immunotherapy in cancer treatment uses a person’s own immune system to fight the cancer. It’s being hailed as the new frontier in cancer treatment, and the drug Keytruda is revolutionizing cancer treatment.
Both studies, published in the New England Journal of Medicine and presented at the annual meeting of the Society of Gynecologic Oncology, showed a significant increase in progression-free survival in people with advanced or recurrent endometrial cancer when they were given immunotherapy and chemotherapy at the same time, instead of just chemotherapy.
Read MoreThe study separated participants into those with mismatch repair-deficiency disease (dMMR), meaning gene mutations are present, and those with mismatch repair-proficient disease (pMMR), meaning mutations are not present. DMMR patients who received immunotherapy and chemotherapy saw a 70% reduction in risk of disease progression at the 12-month follow up. PMMR patients who received the immunotherapy-chemotherapy combo lived on average 13.1 months without their cancer progressing. That’s compared to 8.7 months for those who received only chemotherapy.
PMMR disease makes up “a large chunk of endometrial cancer patients,” said Dr. Ramez Eskander, lead author of the study and gynecologic oncologist at UCSan Diego Health. He added that experts in the field “haven’t been able to identify effective theraputic strategies” for this population.
But with this study, the researchers “saw a 46% reduction in the risk of disease progression or death” for PMMR patients.
“Hopefully these findings will translate into our ability to incorporate immunotherapy for both the DMMR and the PMMR patients,” Dr. Eskander said.
“The magnitude of the benefit that was seen for many of these patients was profound,” said Dr. Carol Aghajanian, chief of Gynecologic Medical Oncology at Memorial Soan Ketting Cancer Center. Dr. Aghajanian oversaw the trial and was the study’s senior author.
This study was a double-blind, placebo-controlled, randomized, phase 3 trial with 816 participants.
The second study combined the immunotherapy drug dostarlimab (brand name Jemperli) with the standard chemo treatment and found similar “significantly increased progression-free survival among patients with primary advanced or recurrent endometrial cancer, with a substantial benefit” for dMMR patients with tumors that had a high precentage of mutations.
This study was a phase 3, global, double-blind, randomized, placebo-controlled trial with 494 participants.
READ MORE: Participating in Clinical Trials
What Is Endometrial Cancer?
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 mentrual cycle, the hormone estrogen causes endometrium to thicken and, if there is no pregnancy, the hormone progresterone causes the endometrial lining to shed and become the menstrual flow.
There are a few kinds of endometrial cancer, also called endometrial carcinoma. Those types include:
- Adenocarcinoma, which is the most common type
- Uterine carcinosarcoma or CS
- Squamous cell carcinoma
- Small cell carcinoma
- Transitional carcinoma
- Serous carcinoma
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
- Obesity
- 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.
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 transvaginal 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, 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 tendancy 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
- Chemotherapy
- Hormone therapy
- Targeted therapy, which includes immunotherapies like the ones used in the studies above
WATCH: Immunotherapy Gave Me Back My Life
What Is Immunotherapy?
Immunotherapy in cancer treatment uses a person’s own immune system to fight the cancer. It’s being hailed as the new frontier in cancer treatment.
While there are many immunotherapy options, Keytruda is revolutionizing the cancer treatment world as it is gaining more and more U.S. Food and Drug Administration approvals to treat various types of cancers. In fact, in 2021 alone, Keytruda was approved 15 times to treat different types of cancers, from early-stage breast cancer to kidney cancer.
Most recently, Keytruda was approved by the FDA for the adjuvant treatment (additional cancer treatment given after the primary treatment) of patients with renal cell carcinoma at an intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection (removal) of metastatic lesions.
While immunotherapy drugs are gaining more popularity, it’s important to know that, as with any drug, they can come with side effects.
“Keytruda is not for everyone,” Dr. Anna Pavlick, professor in the Division of Hematology & Medical Oncology at Weill Cornell Medicine, told SurvivorNet.
She often has patients request the immunotherapy drug Keytruda in response to a commercial they have seen. While it can be an effective immunotherapy, it can also cause severe immune-related adverse effects in certain patients.
Common side effects of Keytruda include feeling tired, pain, rash, diarrhea, fever, cough, decreased appetite, itching, shortness of breath, constipation, and nausea.
And the researchers that studied the combination of dostarlimab (brand name Jemperli) with chemotherapy noted that some participants experienced nausea, alopecia, and fatigue.
What’s Next for Endometrial Cancer Treatment?
While the results of these two studies are promising and were welcomed by the health community, using immunothetrapy as a first-line treatment is not currently the standard of care for endometrial cancer patients.
The Food and Drug Administration would need to approve the use of immunotherapy as a first line treatment for this to happen.
And Dr. Eskander is looking forward to the future.
“Our task is to say, this is an incredible accomplishment, how can we capitalize on this? … How can we improve on these outcomes?” Dr. Eskander said.
Dr. Aghajanian that these findings open the door, but more work is needed. “Despite it being the fourth-most common cancer among women, endometrial cancer is ranked 24th in terms of the amount of funding it receives from the National Cancer Institute,” she said. “There is still so much we don’t know.”
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