Immunotherapy and targeted therapy for endometrial cancer

Targeted therapies and immunotherapies are mainly used to treat advanced or recurrent endometrial cancer. FDA approved drugs are listed below. Clinical trials using these agents may also be available for treatment of endometrial cancer.

Immunotherapies 

Immunotherapies are cancer treatments that help the body’s immune system detect and attack cancer cells. The most common type of  immunotherapies used for endometrial cancer are called immune checkpoint inhibitor. These are most often used to treat advanced or metastatic endometrial cancer with biomarkers known as MSI-H and dMMR. People with Lynch syndrome often develop cancers with these biomarkers.

• Jemperli (dostarlimab) is used in combination with chemotherapy as first line treatment for MSI-H or dMMR advanced endometrial cancer. 
• Jemperli is used alone to treat MSI-H or dMMR advanced or recurrent endometrial cancer, which came back or got worse after platinum chemotherapy. 
• Keytruda is used alone to treat MSI-H or dMMR advanced or recurrent endometrial cancer, in people whose cancer came back or got worse after previous treatment and who are not candidates for curative surgery or radiation. 
• Keytruda is used alone to treat advanced cancers with the biomarker tumor mutational burden-High (TMB-H) that have progressed after treatment and for which there are no other treatment options.
• Keytruda (pembrolizumab) is used to in combination 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 therapies are designed to attack or kill cancer cells, while sparing normal cells as much as possible. These therapies are often designed to target abnormal proteins, receptors or genes that are found in high quantities in cancer cells or the surrounding tissue.  

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
Jemperli (dostarlimab)	Immune checkpoint inhibitor Immune checkpoint inhibitor	Recurrent or advanced endometrial cancer	In combination with chemotherapy, followed by Jemperli alone to treat primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H)	Microsatellite Instability High (MSI-H) or Mismatch Repair Deficiency (MMR-D)
		Recurrent or advanced endometrial cancer	For treatment of recurrent or advanced endometrial cancer that is mismatch repair deficient (dMMR) that has progressed on or following a prior platinum-containing regimen	VENTANA MMR RxDx Panel
Keytruda (pembrolizumab)	Immune checkpoint inhibitor	Advanced endometrial cancer	For the treatment of MSI-H or dMMR advanced or recurrent endometrial cancer that came back or got worse after previous 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 dMMR
Lenvima (lenvatinib)	Tyrosine kinase inhibitor	Advanced endometrial cancer	Combined with pembrolizumab, for the treatment of patients whose cancer has progressed after treatment and who are not candidates for surgery or radiation	Tumor is not MSI-H or dMMR
Vitrakvi (larotrectinib)	Kinase inhibitor	Metastatic solid tumors	For treatment in metastatic solid tumors for which there are no other treatment options	NTRK fusion