KRAS Testing for Colorectal Cancer

Is Testing Right for Me? I Have My Test Results

KRAS Testing for Colorectal Cancer

Treating Advanced Colon Cancer

Several different treatments are available for colon cancer that has spread, or metastasized. Surgery to remove the metastasized cancer may be possible, depending on where the cancer has spread. Whether or not surgery is possible, most people will be treated with some combination of chemotherapy and/or targeted therapy.

The discovery and approval of new treatments for advanced colon cancer holds much promise. Newer drugs try to maximize the good effects of therapy while minimizing the risks. Treatment choices depend on how effective surgery and chemotherapy are likely to be, how well chemotherapy is tolerated, and specific tumor characteristics that predict how some therapies may work. Available treatments work well in many people to fight advanced colon cancer.

Chemotherapy

Most people with advanced colon cancer are treated with chemotherapy of some kind. Chemotherapy works by killing all fast-growing cells in the body. Because cancer cells grow at a fast rate, they are very vulnerable to chemotherapy. The advantage of chemotherapy is that it can travel throughout the body and can kill cancer cells that have spread. Unfortunately, chemotherapy also kills healthy cells. The damage to healthy cells is what leads to the side effects and risks of chemotherapy.

Chemotherapy is commonly used to treat advanced colon cancer. Many drug choices and strategies are available. Chemotherapy may be given as a single drug or a combination of drugs that work together. Combining drugs may help destroy more cancer cells and might lower the risk of cancer becoming resistant to treatment. There are two main approaches to chemotherapy for advanced colon cancer: conservative sequential therapy and combination therapy.

Conservative, Sequential Therapy

Conservative, sequential therapy starts with using one chemotherapy drug (monotherapy) — usually 5-fluorouracil (5-FU) or capecitabine. If cancer worsens on monotherapy, treatment is then followed up with combination therapy.

Combination Therapy

Combination therapy may also be used right from the start. Regardless of when therapy starts, one of three main combinations of chemo drugs is given.

  1. FOLFIRI (a combination of 5-FU, leucovorin (LV), and irinotecan)
  2. FOLFOX (a combination of oxaliplatin, 5-FU, and LV)
  3. XELOX (a combination of capecitabine and oxaliplatin)

Each approach to chemo has its own strengths and weaknesses. Your doctor will figure out the best drug(s), doses, and schedule for you. Following those recommendations as closely as possible will maximize the chance that chemotherapy works.

If your cancer treatment includes 5-FU, you may also be interested in testing for DPD deficiency, a genetic change that can impact how well you respond to that drug. (Read more about  DPD deficiency testing for 5-FU response.

For more information, see:

Targeted Therapy

Targeted therapies are drugs that interfere with specific cell activities to stop cancer from growing or spreading. Cancer happens when a cell loses the ability to control basic activities like growth and development. As the processes that cause cancer or allow it to grow are better understood, new therapies that target these processes can be developed. The action of the drug is more focused on the cancer cells — unlike chemotherapy that targets all fast-growing cells — so there are usually fewer side effects and risks.

Targeted therapy for advanced colon cancer is becoming more common and effective. There are currently two kinds of targeted drugs:

  1. EGFR (epidermal growth factor receptor) targeted antibodies
  2. VEFG (vascular endothelial growth factor) targeted antibodies

EGFR-Targeted Therapy

EGFR-targeted therapy, like Erbitux® (generic cetuximab) or Vectibix® (generic panitumumab), blocks the epidermal growth factor receptor (EGFR) from sending messages into the cell to grow or spread to other parts of the body. Without these messages, the cells eventually die. EGFR-targeted therapy targets epithelial cells. Epithelial cells line the outside and inside surfaces of the body — like the skin and inside the lungs, stomach, and colon. EGFR-targeted therapy stops colon cancer epithelial cells from thriving.

EGFR-targeted therapy works very well for many people with advanced colon cancer, but it doesn't work for about 40% of people. In fact, some patients have done worse when receiving EGFR-targeted therapy. Researchers now know that many people who don't respond well have a KRAS gene mutation in their tumor.

Now, all people who are considering EGFR-targeted therapy should have KRAS gene mutation testing on their tumor before starting therapy. The EGFR-targeted therapies — Erbitux® (generic cetuximab) or Vectibix® (generic panitumumab) — should only be used for people without a KRAS mutation in their colorectal cancer tumor. Recent studies also suggest that EGFR-targeted therapies do not work on tumors with a mutation in the BRAF gene. For this reason, BRAF mutation testing is now recommended for tumors without a KRAS mutation.

EGFR-targeted therapy may be prescribed alone for patients who are intolerant or want to avoid chemotherapy.

  • Erbitux® (cetuximab) can be used with irinotecan chemotherapy to treat advanced colon cancer. Adding cetuximab to chemotherapy lets some patients begin responding to chemotherapy again, when they previously stopped responding.
  • Vectibix® (panitumumab) is approved to use alone in patients with advanced colon cancer for whom standard chemotherapy (e.g. fluoropyrimidine, oxaliplatin, and irinotecan) hasn't worked.

Because EGFR-targeted therapy affects epithelial cells, many of the most common side effects involve the skin — including an acne-like rash on the face and dry, itchy skin. Researchers believe that once the acne-like rash appears, it means that enough epidermal growth factor receptors have been blocked by the therapy. The therapy is working. Because of this, some doctors are now 'dosing to rash', or actually using the signs of the acne rash to tell them when you've reached an ideal, therapeutic dose.

VEGF-Targeted Therapy

VEGF-targeted therapy, like Avastin® (generic bevacizumab), blocks vascular endothelial growth factors (VEGF) from growing new networks of blood vessels. By blocking the action of VEGF, the tumor can't make new blood vessels to feed it. It is starved of nutrients, which stops tumor growth and spreading.

VEGF-targeted therapy can be used together with chemotherapy, as a first choice treatment or once other treatments haven't worked. Avastin® shouldn't be combined with EGFR-targeted therapy. Avastin treatment has been shown to help patients with advanced stage colon cancer, including patients with or without a KRAS mutation in their tumors. One recent study suggested that Avastin may work a little better for those without a KRAS mutation, although more research is needed before we know for sure.

See the National Cancer Institute's Targeted Cancer Therapies: Questions and Answers for more information.
Next: Resources

Do you have advanced colorectal cancer?

Yes

No

Are you considering or are you on anti-EGFR therapy (such as Erbitux® or Vectibix®)?

Yes

No

KRAS gene testing is not likely to be useful for you.

Current medical guidelines from the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) recommend KRAS gene testing for people with advanced colorectal cancer who are considering anti-EGFR therapy. Although other tumor types have KRAS mutations, KRAS gene testing is only recommended for colorectal cancer.

KRAS gene testing may be useful for you.

Current medical guidelines from the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) recommend that genetic testing for KRAS mutations should be done for all patients considering or who have recently begun EGFR-targeted therapy with Erbitux® (cetuximab) or Vectibix® (panitumumab) who have advanced colorectal cancer.

KRAS testing can help predict if you will respond to a treatment for colon cancer called EGFR-targeted therapy (Erbitux® or Vectibix®). Patients with a KRAS mutation in their tumor should avoid treatment with these drugs.

The table below sums up how test results can change your care.

Possible Test Results and What They Mean

Test Result Category Chance To Get This Result What This Result Means
KRAS mutation positive About 40%
  • Your colon cancer is not likely to respond to EGFR-targeted therapy.
  • Anti-EGFR therapy may make your condition worse.
  • Medical guidelines recommend avoiding treatment with Erbitux® or Vectibix®.
  • Other kinds of therapy may work better for your tumor.
KRAS mutation negative About 60%
  • Your colon cancer has a good chance of responding to EGFR-targeted therapy.
  • Depending on your situation, EGFR-targeted therapy may be used alone or combined with chemotherapy.
  • If your tumor didn't respond to earlier chemotherapy, or if chemotherapy has stopped working, you may benefit from the addition of EGFR-targeted therapy.

KRAS gene testing may not be useful for you, because you don't have advanced colorectal cancer. Advanced colorectal cancer is the only cancer for which KRAS gene testing is recommended before starting anti-EGFR therapy.

Erbitux®, an anti-EGFR therapy, is also approved for the treatment of certain head and neck cancers. However, current medical guidelines do not recommend KRAS gene testing before starting Erbitux® for these types of cancers.

Current medical guidelines from the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) recommend KRAS gene testing for people with advanced colorectal cancer who are considering anti-EGFR therapy. Research is being done to find out whether KRAS gene testing might be helpful for other tumor types, but at this time it is not recommended for other cancer types.

KRAS gene testing may not provide information useful to you because you are not considering anti-EGFR therapy.

Current medical guidelines from the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) recommend KRAS gene testing before starting treatment for all patients with advanced colorectal cancer. However, KRAS gene testing is mostly useful for deciding whether anti-EGFR therapy (Erbitux® or Vectibix®) is appropriate treatment. If anti-EGFR therapy is not being considered for treatment of your cancer, KRAS gene testing probably won't provide you useful information.