Drugs that target blood vessel formation (VEGF)
Vascular endothelial growth factor (VEGF) is a protein that helps tumors form new blood vessels (a process known as angiogenesis) to get nutrients they need to grow. Drugs that stop VEGF from working can be used to treat some colon or rectal cancers. These include:
- Bevacizumab (Avastin)
- Ramucirumab (Cyramza)
- Ziv-aflibercept (Zaltrap)
These drugs are given as infusions into your vein (IV) every 2 or 3 weeks, in most cases along with chemotherapy. When combined with chemo, these drugs can often help people with advanced colon or rectal cancers live longer.
Possible side effects of drugs that target VEGF
Common side effects of these drugs include:
- High blood pressure
- Extreme tiredness (fatigue)
- Low white blood cell counts (with increased risk of infections)
- Mouth sores
- Loss of appetite
Rare but possibly serious side effects include blood clots, severe bleeding, holes forming in the colon (called perforations), heart problems, kidney problems, and slow wound healing. If a hole forms in the colon it can lead to severe infection and surgery may be needed to fix it.
Another rare but serious side effect of these drugs is an allergic reaction during the infusion, which could cause problems with breathing and low blood pressure.
Drugs that target cancer cells with EGFR changes
Epidermal growth factor receptor (EGFR) is a protein that helps cancer cells grow. Drugs that target EGFR (EGFR inhibitors) can be used to treat some advanced colon or rectal cancers. These include:
- Cetuximab (Erbitux)
- Panitumumab (Vectibix)
Both of these drugs are given by IV infusion, either once a week or every other week.
These drugs typically don't work by themselves in colorectal cancers that have mutations (defects) in the KRAS, NRAS or BRAF gene. Doctors commonly test the tumor for these gene changes before treatment, and only use these drugs in people whose cancer cells don't have these mutations.
One exception to this is when an EGFR inhibitor is combined with the BRAF inhibitor encorafenib (see below). The combination of these two drugs appears to help people with advanced colorectal cancer live longer, even when the cells have one of these gene mutations.
Possible side effects of drugs that target EGFR
The most common side effects of these drugs are skin problems such as an acne-like rash on the face and chest during treatment, which can sometimes lead to infections. An antibiotic cream or ointment may be needed to help limit the rash and related infections. Developing this rash often means the cancer is responding to treatment. People who develop this rash often live longer, and those who develop more severe rashes also seem to respond better than those with a milder rash. Other side effects can include:
A rare but serious side effect of these drugs is an allergic reaction during the infusion, which could cause problems with breathing and low blood pressure. You may be given medicine before treatment to help prevent this.
Drugs that target cells with BRAF gene changes
A small portion of colorectal cancers have changes (mutations) in the BRAF gene. Colorectal cancer cells with these changes make an abnormal BRAF protein that helps them grow. Some drugs target this abnormal BRAF protein.
If you have colorectal cancer that has spread, your cancer will likely be tested to see if the cells have a BRAF gene change known as BRAF V600E, which can cause the cell to make an abnormal BRAF protein.
Encorafenib (Braftovi) is a BRAF inhibitor - a drug that attacks the abnormal BRAF protein. This drug, when given with an EGFR inhibitor (see above), can shrink or slow the growth of colorectal cancer in some people whose cancer has spread. The combination of these two drugs also appears to help people with advanced colorectal cancer live longer.
This drug is taken as pills or capsules, once a day.
Common side effects can include skin thickening, diarrhea, rash, loss of appetite, abdominal pain, joint pain, fatigue, and nausea.
Some people treated with a BRAF inhibitor might develop new squamous cell skin cancers. These cancers can often be treated by removing them. Still, your doctor will want to check your skin regularly during treatment and for several months afterward. You should also let your doctor know right away if you notice any new growths or abnormal areas on your skin.
Drugs that target cells with HER2 changes
In a small percentage of people with colorectal cancer, the cancer cells have too much of a growth-promoting protein called HER2 on their surface. Cancers with increased levels of HER2 are called HER2-positive. Drugs that target the HER2 protein can often be helpful in treating these cancers.
Drugs of this type that might be used to treat HER2-positive colorectal cancer include:
- Trastuzumab (Herceptin, other names)
- Pertuzumab (Perjeta)
- Tucatinib (Tukysa)
- Lapatinib (Tykerb)
- Fam-trastuzumab deruxtecan (Enhertu)
For advanced, HER2-positive colorectal cancer that has already been treated with chemotherapy, the most common targeted drug regimens include trastuzumab plus either tucatinib, lapatinib, or pertuzumab.
Among these drugs, only tucatinib is FDA approved specifically to treat colorectal cancer at this time. The others are approved to treat other types of cancer, so doctors can prescribe them off-label for colorectal cancer. Still, it’s important to check with your insurance provider before getting these drugs to make sure they are covered.
The side effects of HER2 targeted drugs tend to be mild overall, but some can be serious, and different drugs can have different possible side effects. Discuss what you can expect with your doctor.
Some of these drugs can cause heart damage during or after treatment, which might lead to congestive heart failure. Because of this, your doctor will likely check your heart function (with an echocardiogram or a MUGA scan) before treatment, and regularly while you are getting any of these drugs. Let your doctor know if you develop symptoms such as shortness of breath, a fast heartbeat, leg swelling, and severe fatigue.
Some of these drugs can cause severe diarrhea, so it’s very important to let your health care team know about any changes in bowel habits as soon as they happen.
Lapatinib and tucatinib can also cause hand-foot syndrome, in which the hands and feet become sore and red, and may blister and peel.
Lapatinib and tucatinib can cause liver problems. Your doctor will do blood tests to check your liver function during treatment. Let your health care team know right away if you have possible signs or symptoms of liver problems, such as itchy skin, yellowing of the skin or the white parts of your eyes, dark urine, or pain in the right upper belly area.
Fam-trastuzumab deruxtecan can cause serious lung disease in some people, which might even be life threatening. 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.
Drugs that target cells with NTRK gene changes
A very small number of colorectal cancers have changes in one of the NTRK genes. This causes them to make abnormal TRK proteins, which can lead to abnormal cell growth and cancer.
Larotrectinib (Vitrakvi) and entrectinib (Rozlytrek) are drugs that target the TRK proteins. These drugs can be used to treat advanced cancers with NTRK gene changes that are still growing despite other treatments.
These drugs are taken as pills, once or twice daily.
Common side effects of these drugs can include dizziness, fatigue, nausea, vomiting, constipation, weight gain, and diarrhea.
Less common but serious side effects can include abnormal liver tests, heart problems, and confusion.
Other targeted therapy drugs
Regorafenib (Stivarga) is a type of targeted therapy known as a multikinase inhibitor. Kinases are proteins on or near the surface of a cell that carry important signals to the cell’s control center. Regorafenib blocks several kinase proteins that either help tumor cells grow or help form new blood vessels to feed the tumor. Blocking these proteins can help stop the growth of cancer cells.
This drug can be used to treat advanced colorectal cancer, typically when other drugs are no longer helpful. It's taken as a pill.
Common side effects include fatigue, rash, hand-foot syndrome (redness and irritation of the hands and feet), diarrhea, high blood pressure, weight loss, and abdominal pain.
Less common but more serious side effects can include severe bleeding or perforations (holes) in the stomach or intestines.