No Benefit with Erbitux in KRAS Mutated Tumors

Patients whose colorectal cancer tumors had a mutation in the KRAS gene had no benefit from treatment with Erbitux® (cetuximab).  They lived no longer after Erbitux treatment began than patients who had no Erbitux.

Scientists analyzed nearly 400 tumor samples from patients with colorectal cancer for changes in the KRAS gene.  The patients were part of a randomized study that compared treatment with Erbitux alone (monotherapy) to the best supportive care.  Patients had all been previously treated with 5FU or Xeloda® (capecitabine), Eloxatin® (oxaliplatin), and Camptosar® (irinotecan) and had their cancer get worse.

Mutations in the KRAS gene were found in more than 43 percent of tumors.

Among patients with normal or wild-type KRAS, there were significant differences between those who received Erbitux and those who didn’t:

  • Median overall survival time increased from 4.8 months to 9.5 months.
  • Median time before cancer got worse or progressed increased from 1.9 months to 3.7 months.

However, for patients with mutated KRAS there was no difference in time until cancer progressed or overall survival time with Erbitux treatment.

In the group of patients who were receiving supportive care, but not Erbitux, there was no difference in survival between those with KRAS mutations or wild-type KRAS.

Christos S. Karpetis and his colleagues concluded,

Patients with a colorectal tumor bearing mutated K-ras did not benefit from cetuximab, whereas patients with a tumor bearing wild-type K-ras did benefit from cetuximab.The mutation status of the K-ras gene had no influence on survival among patients treated with best supportive care alone.

Speaking to HealthDay News, Dr. Karapetis said,

We believe that, in the context of pre-treated advanced bowel cancer, the K-ras mutation status of the cancer should be determined before using cetuximab, and cetuximab should only be given to patients with tumors that do not have the mutation.

This study has been previously reported at medical conferences, but its publication in the peer-reviewed New England Journal of Medicine adds strength to its conclusions.

The entire study that showed Erbitux to be superior to best supportive care in advanced colorectal cancer that had progressed on standard treatments was published last year in the New England Journal of Medicine.

You can find additional information about KRAS mutations and treatment with EGFR inhibitors Erbitux and Vectibix on the C3 website.

SOURCE: Karapetis et al.,New England Journal of Medicine, Volume 359, Number 17, October 23, 2008.

Disclosure: C3 has accepted funding for projects and educational programs from ImClone and Bristol Myers Squibb in the form of unrestricted educational grants. C3 has ultimate authority over website content.

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