Targeted Therapy for Colorectal Cancer

As researchers learn more about changes in cells that cause colon or rectal cancer, they have developed new types of drugs to specifically target these changes. Targeted drugs work differently from chemotherapy (chemo) drugs. They sometimes work when chemo drugs don’t, and they often have different side effects. They can be used either along with chemo or by themselves if chemo is no longer working.

Like chemotherapy, these drugs enter the bloodstream and reach almost all areas of the body, which makes them useful against cancers that have spread to distant parts of the body. 

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)
  • Bleeding
  • Low white blood cell counts (with increased risk of infections)
  • Headaches
  • Mouth sores
  • Loss of appetite
  • Diarrhea

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 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 who don't have these mutations. One exception to this is when cetuximab 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 with one of these 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:

  • Headache
  • Tiredness
  • Fever
  • Diarrhea

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

Fewer than 10% 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 there is an abnormal BRAF gene. Drugs that target the abnormal BRAF protein (BRAF inhibitors) aren’t likely to work on colorectal cancers that have a normal BRAF gene.

BRAF inhibitors

Encorafenib (Braftovi) is a drug that attacks the abnormal BRAF protein directly.

This drug, when given with cetuximab (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 of encorafenib with cetuximab 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.

Other targeted therapy drugs

Regorafenib (Stivarga) is a type of targeted therapy known as a kinase 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 is 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.

Newer treatment options

Some colon or rectal cancers that have spread might be tested for other gene mutations to see if different targeted drug combinations may be helpful. To learn about these newer treatment options, see What’s New In Colorectal Cancer Research?

More information about targeted therapy

To learn more about how targeted drugs are used to treat cancer, see Targeted Cancer Therapy.

To learn about some of the side effects listed here and how to manage them, see Managing Cancer-related Side Effects.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Kelly SR and Nelson H. Chapter 75 – Cancer of the Rectum. In: Niederhuber JE, Armitage JO, Dorshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, Pa. Elsevier: 2020.

Lawler M, Johnston B, Van Schaeybroeck S, Salto-Tellez M, Wilson R, Dunlop M, and Johnston PG. Chapter 74 – Colorectal Cancer. In: Niederhuber JE, Armitage JO, Dorshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, Pa. Elsevier: 2020.

Libutti SK, Saltz LB, Willett CG, and Levine RA. Ch 62 - Cancer of the Colon. In: DeVita VT, Hellman S, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 11th ed. Philadelphia, Pa: Lippincott-Williams & Wilkins; 2019.

Libutti SK, Willett CG, Saltz LB, and Levine RA. Ch 63 - Cancer of the Rectum. In: DeVita VT, Hellman S, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 11th ed. Philadelphia, Pa: Lippincott-Williams & Wilkins; 2019.

National Cancer Institute. Physician Data Query (PDQ). Colon Cancer Treatment. 2020. Accessed at https://www.cancer.gov/types/colorectal/patient/colorectal-treatment-pdq on February 19, 2020.

National Cancer Institute. Physician Data Query (PDQ). Rectal Cancer Treatment. 2020. Accessed at https://www.cancer.gov/types/colorectal/patient/colorectal-treatment-pdq on February 19, 2020.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. V.1.2020. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf on Feb 19, 2020.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Rectal Cancer. V.1.2020. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf on Feb 19, 2020.

Riley JM, Cross AW, Paulos CM, et al. The clinical implications of immunogenomics in colorectal cancer: A path for precision medicine. Cancer. 2018 Jan 9.

Wright M, Beaty JS, Ternent CA. Molecular Markers for Colorectal Cancer. Surg Clin North Am. 2017;97(3):683-701.

References

Kelly SR and Nelson H. Chapter 75 – Cancer of the Rectum. In: Niederhuber JE, Armitage JO, Dorshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, Pa. Elsevier: 2020.

Lawler M, Johnston B, Van Schaeybroeck S, Salto-Tellez M, Wilson R, Dunlop M, and Johnston PG. Chapter 74 – Colorectal Cancer. In: Niederhuber JE, Armitage JO, Dorshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, Pa. Elsevier: 2020.

Libutti SK, Saltz LB, Willett CG, and Levine RA. Ch 62 - Cancer of the Colon. In: DeVita VT, Hellman S, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 11th ed. Philadelphia, Pa: Lippincott-Williams & Wilkins; 2019.

Libutti SK, Willett CG, Saltz LB, and Levine RA. Ch 63 - Cancer of the Rectum. In: DeVita VT, Hellman S, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 11th ed. Philadelphia, Pa: Lippincott-Williams & Wilkins; 2019.

National Cancer Institute. Physician Data Query (PDQ). Colon Cancer Treatment. 2020. Accessed at https://www.cancer.gov/types/colorectal/patient/colorectal-treatment-pdq on February 19, 2020.

National Cancer Institute. Physician Data Query (PDQ). Rectal Cancer Treatment. 2020. Accessed at https://www.cancer.gov/types/colorectal/patient/colorectal-treatment-pdq on February 19, 2020.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. V.1.2020. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf on Feb 19, 2020.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Rectal Cancer. V.1.2020. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf on Feb 19, 2020.

Riley JM, Cross AW, Paulos CM, et al. The clinical implications of immunogenomics in colorectal cancer: A path for precision medicine. Cancer. 2018 Jan 9.

Wright M, Beaty JS, Ternent CA. Molecular Markers for Colorectal Cancer. Surg Clin North Am. 2017;97(3):683-701.

Last Revised: June 29, 2020

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