CHICAGO -- Changes in a human gene tied to colon cancer can be used to determine in advance whether a patient will benefit from treatment with
drug Erbitux, researchers reported Sunday at the American Society of Clinical Oncology (ASCO) annual meeting.
In this study, a genetic test was used to examine a gene known as KRAS in patients with newly diagnosed colon cancer. Patients who had a normal copy of the KRAS gene benefited the most from first-line treatment with Erbitux plus chemotherapy. However, patients with a mutated form of KRAS receive no benefit from Erbitux, researchers said Sunday.
Theses findings bolster earlier research that also showed a direct connection between normal, or wild type KRAS, and better patient response to the class of targeted cancer drugs called EGFR inhibitors. These include ImClone's Erbitux and
In Europe, Vectibix is approved for treatment of advanced colon cancer only in patients with the normal KRAS gene. Friday, European regulators recommended approval of Erbitux as a first-line colon cancer treatment also in patients with normal KRAS.
A Larger or Smaller Market for ImClone?
There is no KRAS testing for colon cancer patients in the U.S. that is mandated by the Food and Drug Administration -- yet. That may change as more clinical evidence gathers, including the data presented today. Already however, a growing number of cancer hospitals and doctors in the U.S. are beginning to independently test for KRAS mutations before starting patients on EGFR inhibitor drugs like Erbitux.
It's estimated that between 30% and 40% of colon cancer patients carry the mutated form of KRAS, which would make them ineligible for treatment with Erbitux.
This has many investors and analysts worried that Erbitux's share of colon cancer sales -- the bulk of ImClone's revenue -- may fall considerably.
ImClone, however, plans to push for wider KRAS testing because it believes the genetic biomarker will actually increase Erbitux sales as more colon cancer patients with normal KRAS are identified and treated with their drug and for a longer period of time, says ImClone CEO John Johnson.
"We've submitted a genomics package
on KRAS to the FDA already because we want patients to get the best therapy that's right for them," said Johnson. "We may lose some patients who have the mutant KRAS, but on balance, I think we'll gain patients because our share of wild-type KRAS patients will increase."
Crystal Clear Results
The Crystal study randomized first-line colon cancer patients to Erbitux plus chemotherapy or chemotherapy alone. Results presented last year showed that the addition of Erbitux to chemo slowed the progression of disease by about one month compared to patients treated with chemo alone.
This year, researchers went back and performed genetic tests on patients enrolled in the Crystal study to determine their KRAS status and to see if that affected treatment outcome with Erbitux.
It did. Amongst all patients with normal KRAS, those that were treated with Erbitux had a 32% relative reduction in the risk of tumor progression compared to patients treated with chemotherapy alone - a statistically significant result.
Median progression-free survival (PFS) for the KRAS-normal patients treated with Erbitux was 9.9 months compared to PFS of 8.7 months for chemo-treated patients. That's a difference of 1.2 months, or about five weeks.
When researchers conducted the same analyses on patients with a mutated form of the KRAS gene, they found that the addition of Erbitux to chemotherapy provided no extra benefit.
"KRAS testing should be routinely conducted in all colorectal cancer patients immediately after diagnosis to ensure the best treatment strategies for the individual patient," said Dr. Eric Van Custem, a Belgian colon cancer expert and the principal investigator of the Crystal study.
On Saturday, two other clinical studies were presented at ASCO that also tied normal KRAS status to a better response to Erbitux.
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