Medicine that is tailored to each patient’s genetic makeup is the future of cancer care. In some cases, it is already making a big difference in the ways patients are treated. Learn about these cutting edge treatments and about emerging findings that will be important for future diagnoses and treatments of colorectal cancer. Discussion led by Carolyn Grande, CRNP, AOCNP.
Personalizing Personalized Medicine (4/25/2011)
KRAS Mutations Match in Almost All Tumors
If there is a KRAS mutation in the primary colon or rectal tumor, there is almost always a matching mutation when that tumor spreads to the liver.
Researchers in the Netherlands tested both tumors for KRAS mutations in over 300 patients whose cancer had spread to their livers.
They found about a third of patients had KRAS mutations and KRAS status matched in 96 percent of the cases, making it possible to test either tumor to make decisions about treatment with Erbitux® (cetuximab) or Vectibix® (panitumumab) Read the rest of this entry »
Mutations are Not All the Same
We are making significant progress in understanding what genetic alterations in tumors really mean.
Over the last two years, we have learned or the first time that there is an alteration in a gene called KRAS in colon cancer, and tumors which have this mutation do not respond to treatment with Erbitux® (cetuximab) or Vectibix® (panitumumab).
This is the first time we have a marker to test for sensitivity of an antibody we have to treat colon cancer.
It is very important to know that patients with tumors who carry a KRAS mutation (alteration) are not doing worse overall. They just don’t have any benefit from an antibody which targets the Epithelial Growth Factor Receptor (EGFR). Read the rest of this entry »
All KRAS Mutations May Not Be Alike
There is some evidence that patients having a specific type of KRAS gene mutation may respond better to Erbitux® (cetuximab) chemotherapy than others who have KRAS-gene mutations.
Previous studies have shown that people with KRAS-mutated tumors did not respond to Erbitux®, and practice guidelines now recommend testing all tumor cells for the mutation before starting Erbitux therapy in patients with recurrent, advanced colorectal cancer.
The study, reported in the Oct. 27 Journal of the American Medical Association (JAMA), examined both the data and tissue samples of 579 patients in several studies who received Erbitux® between 2001 and 2008 for chemotherapy-refractory cancer. Those patients with “codon-13” mutations had longer overall and progression-free survival by several months than those with other KRAS mutated tumor cells. Laboratory tests of tumor cell responses also showed that codon-13-mutated cells responded to cetuximab when other KRAS-mutated cells did not.
The study authors concluded that “Evaluation of cetuximab therapy in these tumors in prospective randomized trials may be warranted.”
What it means for patients:
Current evidence has shown the codon-13 type of KRAS mutation to be relatively rare, and more research on therapy response is necessary. It is probably too soon to change recommendations for therapy for those having the codon-13 mutation.
Source: Journal of the American Medical Association, Oct. 27, 2010
Disclosure: The Colorectal Cancer Coalition has received funding from Eli Lilly & Company, Bristol-Myers Squibb and ImClone Systems, the companies that manufacture and market Erbitux, in the form of unrestricted educational grants. The Coalition has ultimate authority over website content.
Adding Erbitux to First Line Chemotherapy Helps Advanced Colorectal Cancer Patients with Wild Type KRAS
Does adding Erbitux to chemotherapy help people whose colorectal cancer has spread beyond the colon or rectum to distant body sites?
The answer is yes, according to a pooled analysis of two large randomized clinical trials comparing chemotherapy alone to chemotherapy plus Erbitux® (cetuximab). However, benefits depend on whether or not patient tumors have mutations of two genes, KRAS and BRAF.
Previous studies have shown that only patients with normal or wild type KRAS get any benefit from EGFR inhibitors Erbitux or Vectibix™ (panitumumab) so a combined analysis of the CRYSTAL and OPUS studies looked only a outcomes in KRAS wild type tumors. In addition, the research team studied the effect of mutations to BRAF.
They found that adding Erbitux to initial chemotherapy improved overall survival time, time until cancers got worse (progression-free survival), the percent of tumors that shrank with treatment (overall response rate) for tumors with wild-type KRAS. The best outcomes were in patients who had both wild-type KRAS and wild-type BRAF. Read the rest of this entry »


