Targeted Therapy for Endometrial Cancer

Targeted therapy drugs are made to attack certain changes in the cancer cells. These drugs work differently from standard chemotherapy (chemo). They tend to have different (and sometimes less severe) side effects.

Targeted therapy drugs are mostly used to treat high-risk endometrial cancers and those that have spread (metastasized) or come back (recurred) after treatment.

Trastuzumab (Herceptin)

Trastuzumab (Herceptin) is a monoclonal antibody, a man-made version of an immune system protein, which targets HER2 (a protein that plays a role in cell growth and division). Adding trastuzumab to chemo is a treatment option for advanced or recurrent HER2-positive endometrial cancer, specifically uterine serous carcinoma and carcinosarcoma. The chemo given with trastuzumab is usually carboplatin and paclitaxel.  Trastuzumab is given as an infusion into the vein (IV) every 3 weeks along with chemo.

Common side effects of trastuzumab include:

• Fever and chills
• Weakness
• Nausea and vomiting
• Cough
• Diarrhea
• Headache

These side effects occur less often after the first dose. A rare but serious side effect is heart damage. Before starting treatment with this drug, your doctor will test your heart function with an echocardiogram or a MUGA scan.

Fam-trastuzumab deruxtecan-nxki (Enhertu)

Fam-trastuzumab deruxtecan (Enhertu) is an antibody-drug conjugate (ADC), which is a HER2 antibody connected to a chemo drug, deruxtecan.  When the ADC is infused into the body, the antibody acts like a homing device, attaching to the HER2 protein on cancer cells and bringing the chemo directly to them.

It can be a treatment option for advanced or recurrent HER2-positive endometrial cancer, after at least 1 other drug has been tried. This drug is given as an infusion into a vein (IV) every 3 weeks.

Common side effects of fam-trastuzumab deruxtecan-nxki include:

• Low blood cell counts (which can increase a person’s risk of infections and bleeding),
• Nausea and vomiting
• Diarrhea or constipation
• Loss of appetite
• Fever
• Feeling tired
• Hair loss

A rare but serious side effect is lung disease and heart damage.  It’s very important to let your doctor or nurse know right away if you’re having symptoms such as coughing, wheezing, trouble breathing, or fever.  Before starting treatment with this drug, your doctor will test your heart function with an echocardiogram or a MUGA scan.

Lenvatinib (Lenvima)

Lenvatinib (Lenvima) is a kinase inhibitor. It helps block tumors from forming new blood vessels, as well as targets some of the proteins in cancer cells that normally help them grow. It is used along with the immunotherapy drug pembrolizumab (Keytruda) to treat some advanced uterine cancers, typically after treatment with carboplatin (a chemo drug) has been tried. Lenvatinib is taken as capsules once a day.

Common side effects of lenvatinib include:

• Diarrhea
• Fatigue
• Joint or muscle pain
• Loss of appetite
• Nausea and vomiting
• Mouth sores
• Weight loss
• High blood pressure
• Swelling in the arms or legs

Less common but more serious side effects can include serious bleeding, blood clots, very high blood pressure, severe diarrhea, holes forming in the intestines, and kidney, liver, or heart failure.

Bevacizumab (Avastin)

For cancers to grow and spread, they need to make new blood vessels to nourish themselves (a process called angiogenesis). Bevacizumab belongs to a class of drugs called angiogenesis inhibitors. This drug attaches to a protein called VEGF (which signals new blood vessels to form) and slows or stops cancer growth.

Bevacizumab can be given for treatment of advanced or recurrent endometrial cancer.  It is often given with chemotherapy as the first treatment option, but it can also be given alone after other drug treatments have been tried. This drug is given as an infusion into a vein (IV) every 2 to 3 weeks.

Common side effects of bevacizuvmab include:

• High blood pressure
• Tiredness
• Bleeding
• Low white blood cell counts
• Headaches
• Mouth sores
• Loss of appetite
• Diarrhea

Rare, but serious side effects include blood clots, severe bleeding, slow wound healing, holes forming in the colon (perforations), and the formation of abnormal connections between the bowel and the skin or bladder (fistulas). If a perforation or fistula forms, it can lead to severe infection and surgery may be needed.

mTOR inhibitors

These drugs block mTOR, a protein in cells that normally helps them grow and divide. They may also stop tumors from developing new blood vessels, which can help limit their growth.

Everolimus (Afinitor)  

Everolimus is usually given with letrozole (aromatase inhibitor) for patients with lower grade, low volume, or slow-growing endometrial cancer that has spread beyond the pelvis or has recurred. It is a pill taken once a day.

Common side effects of everolimus include:

• Mouth sores
• Rash
• Diarrhea
• Nausea
• Feeling weak or tired
• Low blood counts
• Shortness of breath
• Cough

Everolimus can also increase blood lipids (cholesterol and triglycerides) and blood sugars. It can also increase your risk of serious infections, so your doctor will watch you closely.

Temsirolimus (Torisel)

Temsirolimus is given alone for advanced endometrial cancer that has already progressed while the patient took another drug. It is given as an intravenous (IV) infusion, typically once a week.           

Common side effects of temsirolimus include:

• Skin rash
• Weakness
• Mouth sores
• Diarrhea
• Nausea
• Loss of appetite
• Fluid build-up in the face or legs
• Increases in blood sugar and cholesterol levels      

Cabozantinib (Cabometx)

Cabozantinib belongs to a class of drugs called multikinase inhibitors, because they can block several different kinase proteins. These drugs work in two main ways:    

• They help block tumors from forming new blood vessels which the tumors need to grow.

• They target some of the proteins made by cancer cells that normally help them grow.

Cabozantinib are tablets taken once daily.  It is given alone for advanced endometrial cancer that has progressed while the patient took another drug.      

Common side effects of cabozantinib include:

• Fatigue
• Rash
• Loss of appetite
• Diarrhea
• Nausea
• High blood pressure
• Hand foot syndrome (redness, pain, swelling, or blisters on the palms of the hands or soles of the feet)

Rare, but serious side effects include severe bleeding and holes in the intestine.

NTRK inhibitors

A very small number of endometrial cancers have changes in one of the NTRK genes, called NTRK gene fusions. Cells with these gene changes make abnormal TRK proteins, which can lead to abnormal cell growth and cancer.

Larotrectinib (Vitrakyi) or entrectinib (Rozlytrek) are NTRK inhibitors. NTRK inhibitors target and disable the proteins made by the NTRK genes. This drug can be used for advanced endometrial cancer.

These drugs are pills taken once or twice daily.

Common side effects of NTRK inhibitors include:

• Abnormal liver test results
• Decreased white blood cell and red blood cells
• Muscle and joint pain
• Tiredness
• Diarrhea or constipation
• Nausea and vomiting
• Stomach pain 

Rare but serious side effects can include mental changes, such as confusion, changes in mood, and changes in sleep; liver damage; changes in heart rhythm and/or function; vision changes; and harm to a fetus.