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The Importance of K-ras Testing in Colorectal Cancer
- Anti-EGFR therapies are commonly used in treating patients with advanced colon cancer
- These therapies heavily rely on blocking the EGFR signaling pathway
- Recent data strongly suggest the evaluation of downstream markers, such as K-ras, are important in selecting which patient will respond to therapy
- Patients with mutations in the K-ras oncogene are less likely to respond to anti-EGFR therapies
K-ras Mutation Testing 3,4
- An estimated 108,070 cases of colon and 40,740 cases or rectal cancer are expected to occur in 2008
- Colorectal cancer is the 3rd most common cancer and 2nd most common cause of cancer-related deaths
- An estimated 49,960 deaths from colon and rectum cancer are expected to occur in 2008, accounting for 9% of all cancer deaths
Monoclonal antibodies approved to treat mCRC:
- Avastin® (bevacizumab) blocks the growth of blood vessels to the tumor
- Erbitux® (cetuximab) and Vectibix® (panitumumab) block the effect of hormone-like factors that promote cancer cell growth1
EGFR Signaling Pathway
Molecular Marker EGFR Pathway
K-ras Testing is Essential Prior to Anti-EGFR Therapy
The anti-EGFR antibodies show activity in multiple tumor types. However, responses are seen only in the subset of patients lacking a K-ras mutation (wild-type K-ras)
Wild-type K-ras is Required for Monotherapy Efficacy 1
- Results from pivotal "408" trial demonstrate panitumumab monotherapy was significantly more effective than best supportive care in treating mCRC patients
- The treatment effect on progression-free survival (PFS) in the wild-type K-ras group was significantly greater than in the mutant group
- Response rates to panitumumab were much greater (17% vs. 0%) for the wild-type group. Wild-type K-ras patients also had longer overall survival
Wild-type K-ras is Required for Combination Therapy Efficacy2
- CRYSTAL was a Phase III study in first-line mCRC which compared cetuximab plus FOLFIRI to FOLFIRI alone. The results of this study also noted the K-ras mutation status for the enrolled patient
- Anti-EGFR shows additional PFS benefits in patients with wild-type K-ras in CRC as first-line treatment in combination with chemotherapy
K-ras Mutation Analysis
Summary
- K-ras mutations are detected using polymerase chain reaction on DNA from tumor sections
- Majority of mutations occur at codons 12 and 13
- K-ras mutations can be detected in approximately 30-45% of all patients with colon cancer
- Patients with wild-type K-ras have been shown much greater benefit to anti-EGFR therapies
- Identification of mutations along the K-ras gene suggests that anti-EGFR therapies will not be efficacious in most, if not all, patients
- Avoid unnecessary toxicity, treatment delays and monetary cost to patients who do not respond to anti-EGFR therapies
- Patients should be screened prior to initiating anti-EGFR therapy
The Clarient Difference
- Can be run on FNA samples
- Requires less tissue than many other methodologies
- Reduced quantity not sufficient samples (QNS)
- Rapid turn-around-time (5-7 days)
References
- Amado RG, Wolf M, Peeters M, et al: Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 26(10):1-9, 2008.
- E. Van Cutsem, et al: KRAS status and efficacy in the first-line treatment of patients with metastatic colorectal cancer (mCRC) treated with FOLFIRI with or without cetuximab: The CRYSTAL experience. J Clin Oncol 26: 2008 (May 20 suppl; abstr 2)
- www.cancer.gov/cancertopics/pdq/treatment/colon/HealthProfessional
- www.cancer.org/downloads/STT/2008CAFFfinalsecured.pdf
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