KRAS mutations: effectiveness and patient symptoms with Vectibix treatment

FROM 2008 ORLANDO GI SYMPOSIUM

Not all patients treated with Vectibix® (panitumumab) will respond to it.  In a randomized clinical that compared colorectal cancer treatment with Vectibix alone to the best supportive cancer care, only about ten percent had tumors shrink. All patients in the study had previously gotten worse on standard treatments. In this trial, Vectibix was given alone or as monotherapy.

In an attempt to figure out which patients  were most likely to benefit from Vectibix, researchers measured tumor DNA for a mutation in the KRAS gene. They studied the differences in both treatment outcomes and patient-reported cancer symptoms and quality of life between those patients with mutated KRAS genes and those with normal or wild type KRAS.

About 43 percent of patients had a mutation in the KRAS gene.

Comparing patients with mutated KRAS with wild type KRAS, they found:

Impact on progression-free survival

  • Wild type KRAS: Median time before cancer began to progress for patients on Vectibix was 12.3 weeks compared to 7.3 weeks for best supportive care.
  • Mutated KRAS: Median progression-free survival was not different between the two groups (7.4 weeks for those on Vectibix and 7.3 weeks for those receiving supportive care.)

Impact on response to treatment

  • All patients: 10 percent in group that received Vectibix  had tumors shrink somewhat (partial response) compared to no partial responses in the best supportive care arm.
  • Wild type KRAS: 17 percent partial responses with Vectibix compared to none in supportive care.
  • Mutant KRAS: No partial responses in either the Vectibix group or the group that received best supportive care.

Impact on stable disease

  • All patients: 25 percent had their cancer remain stable during the trial while on Vectibix compared to 10 percent on supportive care.
  • Wild type KRAS: 34 percent had stable disease on Vectibix compared to 10 percent on best supportive care.
  • Mutant KRAS: 12 percent had stable disease on Vectibix compared to 8 percent not receiving the drug.

Impact on quality of life

  • Wild type KRAS: Scores of patient-reported outcomes on quality of life were better for patients receiving Vectibix and their cancer symptoms improved somewhat during treatment.
  • Mutant KRAS: There was no difference in quality of life between the two groups and cancer symptoms and quality of life got worse during treatment.

Overall, the researchers felt that there was no benefit to treating patients with mutated KRAS with Vectibix in this particular setting — when they had gotten worse on all previous standard treatments and when Vectibix was used alone.

There is other research underway to study response to Vectibix earlier in metastatic colorectal cancer treatment and in combination with chemotherapy including the impact of KRAS mutations on that response.

Vectibix is approved by the FDA to treat patients with colon or rectal cancer who had progressed on all other therapies.

R.G. Amado, MD and colleagues concluded in a 2008 GI Symposium abstract that

Panitimumab efficacy in CRC is confined to patients with tumors lacking KRAS mutations. Wild type KRAS patient receiving panitumumab had better colorectal cancer symptoms vs best supportive care patients.

In his presentation, Dr. Amado also pointed out:

KRAS genotyping of tumors should be strongly considered in patients with metastatic colorectal cancer being treated with panitumumab monotherapy.

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Disclosure: Fight Colorectal Cancer has accepted funding for projects and educational programs from Amgen in the form of unrestricted educational grants. Fight CRC has ultimate authority over website content.

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Comments

  1. Kate Murphy says

    Vectibix is approved by the FDA to treat colorectal cancer that has spread beyond the colon and after all other standard treatments have failed.

    It works by blocking a receptor on the surface of the cancer cell (epidermal growth factor receptor or EGFR) making it impossible for the cell to receive signals to divide and the cancer to grow.

    In some patients, cancer cells will die and the tumor will get smaller. In others, the tumor will not grow, but remain stable.

    For some — but not all — patients, Vectibix increases time until the cancer gets worse and also increases survival time. It doesn’t remove all cancer, but it does increase survival time.

    It also appears to improve quality of life.

    It is critical to test the tumor for KRAS mutations since patients whose tumors have mutated KRAS will not benefit from taking Vectibix. They had no better survival or quality of life than patients who did not take the medicine.

    If you have more questions, please call us at the C3 Answer Line (1-877-4CRC-111).

    Kate Murphy, Director of Research Communication at C3: Colorectal Cancer Coalition.

  2. Kendra Falvey says

    I had the KRAS test done last Dec. 5th and it found my tumor has the KRAS mutation. Unfortunately my insurance does not want to cover the cost of this test and it was $4500. BCBS of FL. states it is not FDA approved so they do not cover the cost. The testing company has appealed and it is still ongoing, but my time to file an appeal is running out. Is there anything you can suggest that will help me in my appeal to get them to cover this cost? Thank you.

  3. louisa says

    A friend got treated with panitimumab and the originally colon cancer that was only present in the liver spread like wild fire during that treatment. Before the final scan I questioned if a test like the Kras-gene mutation test really had been performed before delivering the Panitimumab treatment. What questions does one need to ask a doctor to be sure Kras gene mutation has been tested. Is the spread of cancer a proof that the test has not been taken?

  4. Kate Murphy says

    KRAS mutation testing results should be quite clear. Tumor tissue is tested and the answer is either “yes”, KRAS is mutated or “no” it is normal or wild-type.

    A patient can — and probably should — ask for a copy of the test report.

    Unfortunately, having normal KRAS results does not guarantee response to either Vectibix (panitumumab) or Erbitux (cetuximab). While people with mutations in KRAS don’t benefit from these EGFR blocking drugs, only some patients with normal KRAS will benefit.

    It is entirely possible that your friend was tested, was normal, and still had cancer get worse.

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