Targeted therapies are drugs that block the growth of cancer by interfering with the molecules involved in tumor growth and spread. This treatment differs from chemotherapy, which targets any rapidly dividing cells, because targeted therapies are designed to interfere with genes and proteins specific to the malignant cancer. Because of this level of specificity, targeted therapies for colorectal cancer tend to have less severe side effects than chemotherapy. However, while targeted therapies have been shown to be helpful in patients with stage IV cancer, they have not been as helpful in patients with stage III cancer.

Types of Targeted Therapies for Colorectal Cancer

Angiogenesis Inhibitors

This therapy is focused on stopping angiogenesis, which is the process of making new blood vessels. Because a tumor needs the nutrients delivered by blood vessels to grow and spread, the goal of anti-angiogenesis therapies is to “starve” the tumor.

Studies have shown that both older and younger patients are able to benefit from targeted therapies. In addition, the expected side effects are usually manageable in both older and younger patients.

For colorectal cancer, the following targeted therapies may be options:

Bevacizumab (Avastin®)

When bevacizumab is given with chemotherapy, it increases the length of time people with advanced colorectal cancer live. In 2004, the FDA approved bevacizumab along with chemotherapy as the first treatment, or first-line treatment, for advanced colorectal cancer. Recent studies have shown it is also effective as second-line therapy along with chemotherapy. There are two drugs similar to bevacizumab – bevacizumab-awwb (Mvasi) and bevacizumab-bvzr (Zirabev) – that have also been approved by the FDA to treat advanced colorectal cancer. These are called biosimilars.

Regorafenib (Stivarga^®)

This drug is used to treat people with metastatic colorectal cancer who have already received certain types of chemotherapy and other targeted therapies.

Ziv-aflibercept (Zaltrap^®) and ramucirumab (Cyramza^®)

Either of these drugs can be combined with FOLFIRI chemotherapy as a second-line treatment for metastatic colorectal cancer.

Epidermal Growth Factor Receptor (EGFR) Inhibitors

Researchers have found that drugs that block EGFR may be effective for stopping or slowing the growth of colorectal cancer.

Cetuximab (Erbitux®) and Panitumumab (Vectibix®)

Recent studies show that cetuximab and panitumumab do not work as well for tumors that have specific changes, called mutations or alterations, to a gene called RAS. The RAS gene family is a family of genes that make proteins involved in cell signaling pathways that control cell growth and cell death. Mutated (changed) forms of the RAS gene may be found in some types of cancer. These changes may cause cancer cells to grow and spread in the body. Members of the RAS gene family include KRAS, HRAS, and NRAS.

ASCO recommends that all people with metastatic colorectal cancer who may receive an EGFR inhibitor have their tumors tested for RAS and RAF gene mutations. If a tumor has a mutated form of the RAS gene or a specific BRAF mutation (V600E), ASCO and NCCN recommend that patients do not receive EGFR inhibitors. The tumor may also be tested for other molecular markers, including HER2 over-expression and others. These markers do not have FDA-approved targeted therapies yet, but there may be opportunities in clinical trials that are studying these molecular changes.

If you are on an EGFR inhibitor make sure to read about skin toxicity, also known as chemo rash, is a rash caused by this particular treatment.

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Combined Targeted Therapies

encorafenib (Braftovi^®) and cetuximab

Some tumors have a specific mutation, called BRAF V600E, which can be detected by an FDA-approved test. A class of targeted treatments called BRAF inhibitors can be used to treat tumors with this mutation. A combination using the BRAF inhibitor encorafenib (Braftovi^®) and cetuximab may be used to treat people with metastatic colorectal cancer with this mutation who have received at least one previous treatment.

ADAGRASIB (KRAZATI^®) AND CETUXIMAB

Some tumors have a specific KRAS mutation, KRAS G12C, which can be detected by an FDA-approved test. A combination using the KRAS G12C inhibitor adagrasib (Krazati^®) and cetuximab may be used to treat people with locally advanced or metastatic colorectal cancer with this particular mutation, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

Tumor-Agnostic Treatment

Larotrectinib (Vitrakvi^®) and entrectinib (Rozlytrek^®)

Larotrectinib (Vitrakvi^®) and entrectinib (Rozlytrek^®) are types of targeted therapy that are not specific to a certain type of cancer, but focus on a specific genetic change called an NTRK fusion. This type of genetic change is rare but is found in a range of cancers, including colorectal cancer. These medications are approved as treatment for colorectal cancer that is metastatic or cannot be removed with surgery and has worsened with other treatments.

What to Expect Before Receiving Targeted Therapies

Targeted therapies can be administered through an IV or orally in pill- or capsule-form. Typically, monoclonal antibodies are administered through an IV. It depends on the drug and how it will be administered to determine whether you can undergo treatment at home or at a medical facility.

Side Effects of Targeted Therapies

Since targeted therapies are designed to have a more focused action, they tend to have less severe side effects when compared to chemotherapies. However, the actual effects and their severity largely depends on the targeted action in question. And since targeted therapies are a relatively new development in cancer treatment, the long-term effects are still being studied.

Skin Problems

Targeted therapies can sometimes cause skin problems over the course of a few days or weeks, such as a rash or other skin changes. These differ from drug allergies, which start within a few minutes or hours of starting the treatment. Any skin problems should be reported to your oncology team before starting any over-the-counter medicines. Possible instances of this side effect include:

• Sunburnt feeling without the appearance of redness or rash
• Photosensitivity
• Rash
• Dry skin
• Red, sore cuticles
• Hand-foot syndrome
• Changes in hair growth
• Changes in hair or skin color
• Changes in and around the eyes

Other Side Effects of Targeted Therapies

Depending on the action of the targeted therapy being used, you may experience the following side effects:

• High blood pressure
• Bleeding or blood clotting problems
• Slow wound healing
• Heart damage
• Autoimmune reactions
• Swelling

Since targeted therapies can sometimes be considered a form of chemotherapy, you may also experience similar side effects such as:

• Nausea and vomiting
• Diarrhea or constipation
• Mouth sores
• Shortness of breath or trouble breathing
• Cough
• Fatigue
• Headache
• Hair loss
• Damage to organs such as the thyroid gland, liver, or kidneys
• Allergic reactions (while getting an IV drug)
• Increased risks of certain infections