Biomarkers, targeted and immunotherapies for endometrial cancer

This section covers the following topics:

Tumor biomarker testing for treatment selection
Immunotherapy
Targeted therapy

Biomarker tests

Biomarker tests look at samples of blood, tumor or other tissue for changes or abnormalities caused by cancer. These tests can give doctors clues about the cancer, including:

how fast the cancer is growing
which treatments are most likely to work
whether or not the cancer is responding to treatment or growing
whether or not the cancer has come back after remission

Biomarkers for treatment selection

Biomarker tests may be used to select treatments, and help patients avoid side effects from treatments that will not work for them. Biomarker tests used to select a specific treatment are sometimes called "companion diagnostic tests." These tests may be done on tumor tissue or (in many cases) on blood. See our Biomarker Testing section for more information.

Experts recommend testing all endometrial cancers for an abnormality known as MSI-H (“microsatellite instability high") also known as "mismatch repair deficiency" (dMMR or MMR-D).
- MSI-high cancers are common in people with a Lynch syndrome gene mutation. People with advanced or metastatic MSI-high endometrial cancer may respond well to a type of immunotherapy known as an immune checkpoint inhibitor.
- People with advanced, recurrent endometrial cancer that is not MSI-H, may benefit from a combination of the targeted therapy, Lenvima (lenvatinib) and the immunotherapy agent Keytruda.
Examples of additional biomarker tests used in endometrial cancer include:
- A rare type of endometrial cancer—known as a uterine sarcoma—may have a genetic change called an NTRK fusion, which can be found on tumor testing. Endometrial with an NTRK fusion may benefit from the targeted therapy Vitrakvi (larotrectinib).
- A biomarker known as an NTRK fusion is rare in colorectal cancer.
- Estrogen receptor testing is used for advanced and recurrent endometrial cancers.
- Her2neu testing is used to find advanced or recurrent endometrial cancers that may respond to Herceptin.
- Additional tumor biomarker testing may help identify people who are elegible for certain clinical trials.

Immunotherapies

Immunotherapies are cancer treatments that help the body’s immune system detect and attack cancer cells. There are several different categories of immunotherapies.

Keytruda (pembrolizumab) is FDA approved to treat tumors that have MSI-H or dMMR. It can also be used along with the targeted drug lenvatinib in women with advanced endometrial cancers that are not dMMR or MSI-H, usually after other treatments have been tried.

Targeted therapies

Targeted therapy is still fairly new in the treatment of endometrial cancer. Currently, these agents are only prescribed if the cancer has recurred or as part of a clinical trial. Targeted therapies for endometrial cancer include:

Vitrakvi (larotrectinib) is approved for treatment of endometrial cancer that is metastatic or cannot be removed with surgery and has worsened with other treatments. It targets a specific genetic change called an NTRK fusion. This type of genetic change is found in a range of cancers, including a rare type of uterine cancer known as uterine sarcoma.
Lenvima (lenvatinib) helps block tumors from forming new blood vessels. Lenvima can be used along with the immunotherapy drug Keytruda to treat some advanced endometrial cancers, typically after at least one other drug treatment has been tried.
Afinitor (everolimus) is a type of targeted therapy known as an mTOR inhibitor that has been used (off label) to treat some people with advanced endometrial cancer. Afinitor does not have FDA approval for use in endometrial cancer.
Avastin (bevacizumab) helps block tumors from forming new blood vessels. Avastin does not have FDA approval for use in endometrial cancer.

Table of targeted and immunotherapies for endometrial cancer

Name of drug	Type of agent	Cancer stage	Indication	Biomarker
Keytruda (pembrolizumab)	Immune checkpoint inhibitor	Metastatic or unresectable solid tumors	For treatment of solid tumors that have progressed after treatment and for which there are no other treatment options	Microsatellite Instability High (MSI-H) or Mismatch Repair Deficiency (MMR-D)
		Metastatic or unresectable solid tumors	For the treatment of solid tumors that have progressed after treatment and for which there are no other treatment options	Tumor Mutational Burden High (TMB-H)
		Advanced endometrial cancer	Combined with Lenvima (lenvatinib) for patients whose cancer has progressed after treatment and who are not candidates for surgery or radiation	Tumor is not MSI-H or MMR-D
Lenvima (lenvatinib)	Tyrosine kinase inhibitor	Advanced endometrial cancer	Combined with pembrolizumab, for the treatment of women whose cancer has progressed after treatment and who are not candidates for surgery or radiation	Tumor is not MSI-H or MMR-D
Vitrakvi (larotrectinib)	Kinase inhibitor	Metastatic solid tumors	For treatment in metastatic solid tumors where surgical resection is likely to result in severe morbidity, and for which there are no satisfactory alternative treatments or the cancer progressed following treatment	NTRK fusion

All endometrial cancers should be tested for a biomarker known as MSI-H (also called MSI-high, dMMR or MMR-D)
Advanced cancers that are MSI-high may respond well to immunotherapy called immune checkpoint inhibitors.
Cancers in people with Lynch syndrome are often MSI-high.

The following are resources for people who have been diagnosed with endometrial cancer:

Cancer.net is a website from the American Society of Clinical Oncology with expert-reviewed, comprehensive information on endometrial cancer.
The National Comprehensive Cancer Network (NCCN) is an alliance of experts who create guidelines for cancer prevention and treatment.
- NCCN has created a free patient guide for women with endometrial cancer.
The Foundation for Women's Cancer (FWC) is an organization created by the Society of Gynecologic Oncologists, with comprehensive information on endometrial cancer.

The majority of public and private health insurance plans are required to cover cancer diagnosis and treatment; copays, coinsurance and deductibles often apply. Patient costs and coverage for specific doctors, facilities or treatments may vary based on your health plan. Visit our section on Insurance and Paying for Care: Treatment for more information, links to sample appeal letters and other resources.

Some pharmaceutical companies and laboratories have assistance programs that help cover the cost for their medications, tumor testing or genetic testing for an inherited mutation:

Organizations that offer co-pay assistance:

Other resources:

The American Cancer Society provides information and resources on covering the cost of cancer care. Public assistance, such as Medicaid may be available if you are ineligible for other programs.
Needy Meds: Assistance programs to help patients with cost of medications and other healthcare.
Triage Cancer offers tools and resources to help individuals cope with the financial aspects of a cancer diagnosis.

The following studies may be of interest to women with endometrial cancer and an inherited mutation.

Advanced solid tumors of any type

NCT03538028: A Safety and Tolerability Study of INCAGN02385 in Select Advanced Malignancies. The purpose of this study is to determine the safety, tolerability, and preliminary efficacy of INCAGN02385 in participants with advanced malignancies. The study is enrolling people with MSI-H endometrial cancer.
NCT04082572: Pembrolizumab Before Surgery for the Treatment of Mismatch Repair Deficient Locally Advanced Solid Cancers. This trial studies how well the immunotherapy agent, pembrolizumab works before surgery in treating patients with mismatch repair deficient solid cancers that have spread to nearby tissue or lymph nodes (locally advanced). This study may be of particular interest to people with a mutation in a Lynch syndrome gene.
NCT04001101: A Randomized Phase II Study of Anti-PD-1 and Limited Metastatic Site Radiation Therapy Versus Anti-PD-1 Alone for Patients With Microsatellite Instability-high (MSI-H) and Mismatch Repair Deficient (dMMR) Metastatic Solid Tumors. To determine if treatment is improved with the addition of radiation therapy to anti-PD-1 for patients with MSI-H/dMMR metastatic solid tumors. This study may be of particular interest to people with a mutation in a Lynch syndrome gene.
NCT03607890: Study of Nivolumab and Relatlimab in Advanced Mismatch Repair Deficient Cancers Resistant to Prior PD-(L)1 Inhibitor. The purpose of this study is to evaluate the safety and clinical activity of nivolumab and relatlimab in patients with microsatellite instability high (MSI-H) solid tumors refractory to prior PD-(L)1 therapy. This study may be of particular interest to people with a mutation in a Lynch syndrome gene.
NCT04041310: Nous-209 Genetic Vaccine for the Treatment of Microsatellite Unstable Solid Tumors. NOUS-209-01 is a multicenter, open-label, multiple cohorts, First In Humans (FIH) clinical study, designed to evaluate safety, tolerability, and immunogenicity, and to detect any preliminary evidence of anti-tumor activity of Nous-209 genetic polyvalent vaccine. This study may be of particular interest to people with a mutation in a Lynch syndrome gene.
NCT03832569: Study of Pembrolizumab or Placebo Following Surgery in Patients With Microsatellite Instability High (MSI-H) Solid Tumors. This study tests the safety of the drug, pembrolizumab, and to find out how well it works to prevent cancer from coming back in people who have had a solid tumor surgically removed, but still have tumor cells in their blood. This study may be of particular interest to people with a mutation in a Lynch syndrome gene.
NCT02715284: A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors (GARNET). This study may be of particular interest to people with a mutation in a Lynch syndrome gene.
NCT03767348 : Study of RP1 Monotherapy and RP1 in Combination With Nivolumab. RPL-001-16 is a clinical study of RP1 alone and in combination with nivolumab in adult subjects with advanced and/or refractory solid tumors, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), as well as to evaluate preliminary efficacy.This study may be of particular interest to people with a mutation in a Lynch syndrome gene.
NCT03589339: NBTXR3 Activated by Radiotherapy for Patients With Advanced Cancers Treated With An Anti-PD-1 Therapy. The 1100 study is an open-label, Phase I, prospective clinical study to assess the safety of intratumoral injection of NBTXR3 activated by radiotherapy in combination with anti-PD-1 therapy. This study may be of particular interest to people with a mutation in a Lynch syndrome gene.
NCT03517488: A Study of XmAb®20717 in Subjects With Selected Advanced Solid Tumors (DUET-2). This is a Phase 1, multiple dose, ascending dose escalation study to define a MTD/RD and regimen of XmAb20717, to describe safety and tolerability, to assess PK and immunogenicity, and to preliminarily assess anti-tumor activity of XmAb20717 in subjects with selected advanced solid tumors, including endometrial cancers with MSI-H.

Endometrial cancer

NCT02912572: Avelumab in Patients With MSS, MSI-H and POLE-mutated Recurrent or Persistent Endometrial Cancer and of Avelumab/Talazoparib in Patients With MSS Recurrent or Persistent Endometrial Cancer. This research study is evaluating a drug called Avelumab as a possible treatment for recurrent or Metastatic Endometrial Cancer.
NCT03981796: A Study of Dostarlimab (TSR-042) Plus Carboplatin-paclitaxel Versus Placebo Plus Carboplatin-paclitaxel in Patients With Recurrent or Primary Advanced Endometrial Cancer (RUBY). This is a study to evaluate the efficacy and safety of dostarlimab plus carboplatin-paclitaxel in patients with recurrent or primary advanced (Stage III or IV) endometrial cancer.

Visit our Research Search and Enroll Tool to find additional studies.