Targeted Drug Therapy for Kidney Cancer

As researchers learn more about the changes in cells that cause cancer, they have developed drugs that target some of these changes. These targeted drugs are different from standard chemotherapy drugs. They sometimes work when standard chemo drugs don’t, and they often have different side effects.

Targeted drugs are proving to be especially important in kidney cancer, where chemotherapy has not been shown to be very effective.

When might targeted drugs be used?

Treating advanced kidney cancer

All of the targeted drugs below can be used to treat advanced kidney cancers. They can often shrink or slow the growth of the cancer for a time, but it doesn’t seem that any of these drugs can actually cure kidney cancer.

Targeted drugs are most often used one at a time. If one doesn’t work, another can be tried. It’s not yet known if any one of these drugs is clearly better than the others, if combining them might be more helpful than giving them one at a time, or if one sequence is better than another. Studies are being done to help answer these questions.

Adjuvant therapy after surgery

The targeted drug sunitinib (Sutent) can also be used after surgery in people with a high risk of the cancer returning, to help lower the risk that the cancer will come back. This is known as adjuvant therapy.

Targeted drugs used to treat kidney cancer

Most of the targeted drugs used to treat kidney cancer work by blocking angiogenesis (growth of the new blood vessels that feed cancers) or important proteins in cancer cells (called tyrosine kinases) that help them grow and survive. Some targeted drugs affect both.

Drugs that target tumor blood vessel growth (angiogenesis)

Sunitinib (Sutent)

Sunitinib acts by blocking both angiogenesis and growth-stimulating proteins in the cancer cell itself. Sunitinib does this by blocking several tyrosine kinases that are important for cell growth and survival. This drug is taken as a pill daily, typically for 4 weeks on and 2 weeks off. Some doctors might recommend taking it 2 weeks on and 1 week off to reduce side effects.

Sunitinib can be used in people with advanced kidney cancer, as well as in people with a high risk of the cancer returning after surgery, to help lower the risk that the cancer will come back. This is known as adjuvant therapy.

The most common side effects are nausea, diarrhea, changes in skin or hair color, mouth sores, weakness, and low white and red blood cell counts. Other possible effects include tiredness, high blood pressure, congestive heart failure, bleeding, hand-foot syndrome, and low thyroid hormone levels.

Sorafenib (Nexavar)

Sorafenib blocks several tyrosine kinases, similar to the ones blocked by sunitinib. It attacks both blood vessel growth and other targets that help cancer cells grow. It is taken as a pill twice a day.

The most common side effects seen with this drug include fatigue, rash, diarrhea, increases in blood pressure, and redness, pain, swelling, or blisters on the palms of the hands or soles of the feet (hand-foot syndrome).

Pazopanib (Votrient)

Pazopanib is a drug that blocks several tyrosine kinases involved in cancer cell growth and the formation of new blood vessels in the tumor. It is taken as a pill once a day.

Common side effects include high blood pressure, nausea, diarrhea, headaches, low blood cell counts, and hair color change. It can cause lab test results of liver function to become abnormal, but it rarely leads to severe liver damage that could be life threatening. Problems with bleeding, clotting, and wound healing can occur, as well. In rare cases it can also cause a problem with the heart rhythm or even a heart failure. If you are taking this drug, your doctor will monitor your heart with EKGs as well as check your blood tests for liver or other problems.

Cabozantinib (Cabometyx)

Cabozantinib is a drug that blocks several tyrosine kinases, including some that help form new blood vessels.

• It might be used first to treat people with intermediate or poor risk advanced kidney cancer
• It might be used first with the immunotherapy drug, nivolumab, in people with advanced kidney cancer
• It might be used in people with advanced kidney cancer after someone has already tried another drug that blocks angiogenesis or after immunotherapy treatments. 

It is taken as a pill once a day and has shown to help people live longer in certain cases.

Common side effects include diarrhea, fatigue, nausea and vomiting, poor appetite and weight loss, high blood pressure, hand-foot syndrome, and constipation. Less common but more serious side effects can include serious bleeding, blood clots, very high blood pressure, severe diarrhea, and holes forming in the intestines.

Lenvatinib (Lenvima)

Lenvatinib is a kinase inhibitor drug that helps block tumors from forming new blood vessels, as well as targeting some of the proteins in cancer cells that normally help them grow. It can be used along with everolimus (see below) after at least one other treatment has been tried. The combination has been shown to help some people live longer. It can also be used with the immunotherapy drug pembrolizumab as a first treatment in people with advanced kidney cancer. Lenvatinib is taken as capsules once a day.

Common side effects include diarrhea, fatigue, joint or muscle pain, loss of appetite, nausea and vomiting, mouth sores, weight loss, high blood pressure, and 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)

Bevacizumab is an IV drug that works by slowing the growth of new blood vessels. It may help some people with kidney cancer when used with interferon-alfa.

More common side effects include high blood pressure, tiredness, and headaches. Less common but possibly serious side effects include bleeding, blood clots, holes forming in the intestines, heart problems, and slow wound healing.

Axitinib (Inlyta)

Axitinib is a drug that inhibits several tyrosine kinases involved in the formation of new blood vessels. It can be used by itself after at least one other treatment has been tried, or it can be used with certain immunotherapy drugs, like pembrolizumab or avelumab, as the first treatment for people with advanced kidney cancer. Axitinib is taken as a pill twice a day.

Common side effects include high blood pressure, fatigue, nausea and vomiting, diarrhea, poor appetite and weight loss, voice changes, hand-foot syndrome, and constipation. High blood pressure requiring treatment is fairly common, but in a small number of patients it can get high enough to be life-threatening. It can also cause problems with bleeding, clotting, and wound healing. In some patients, lab test results of liver function can become abnormal. Axitinib may also cause the thyroid gland to become underactive, so your doctor will watch your blood levels of thyroid hormone while you are on this drug.

Tivozanib (Fotivda)

Tivozanib is a drug that blocks several tyrosine kinases involved in cancer cell growth and the formation of new blood vessels in the tumor. This drug is taken as a pill daily, typically for 3 weeks on and 1 week off.

It might be used in people with advanced kidney cancer after someone has already tried two or more other systemic drugs such as chemotherapy, targeted therapy, or immunotherapy.

Common side effects include high blood pressure, diarrhea, nausea, poor appetite, cough, mouth sores, feeling tired, and voice changes. Less common but more serious side effects can include heart problems, life threatening high blood pressure, blood clots, bleeding, poor wound healing, abnormal thyroid tests, and damage to the kidney.

Belzutifan (Welireg)

Belzutifan is a type of drug known as a HIF inhibitor. It blocks a protein called hypoxia-inducible factor 2 alpha (HIF-2a), which is involved in both cancer cell growth and the formation of new blood vessels in tumors. This drug is taken as pills, typically once a day.

Belzutifan can be used:

• In people with von Hippel-Lindau (VHL) disease who have kidney cancer and don’t need surgery right away.
• In people with advanced kidney cancer that has already been treated with a different targeted drug and with an immune checkpoint inhibitor (a type of immunotherapy drug).

Common side effects of this drug include low red blood cell counts (anemia), feeling tired and/or dizzy, nausea, headache, increased blood sugar levels, and changes in lab tests showing the drug might be affecting the kidneys. Less common but more serious side effects can include very low red blood cell counts (severe anemia), which might require blood transfusions, and low oxygen levels in the body, for which you might need oxygen therapy or even be admitted to the hospital.

Drugs that target the mTOR protein

Temsirolimus (Torisel)

Temsirolimus works by blocking a protein known as mTOR, which normally helps cells grow and divide. This drug has been shown to be helpful against advanced kidney cancers that have a poorer prognosis because of certain factors and may help some people live longer. It is given as an intravenous (IV) infusion, typically once a week.

The most common side effects of this drug include skin rash, weakness, mouth sores, nausea, loss of appetite, fluid buildup in the face or legs, and increases in blood sugar and cholesterol levels. Rarely, more serious side effects have been reported.

Everolimus (Afinitor)

Everolimus also blocks the mTOR protein. It is used to treat advanced kidney cancers after other drugs such as sorafenib or sunitinib have been tried. It can be used by itself or along with lenvatinib (see above) after at least one other treatment has been tried. Everolimus is taken as a pill once a day.

Common side effects of this drug include mouth sores, an increased risk of infections, nausea, loss of appetite, diarrhea, skin rash, feeling tired or weak, fluid buildup (usually in the legs), and increases in blood sugar and cholesterol levels. A less common but serious side effect is lung damage, which can cause shortness of breath or other problems.