Clinical benefit of high-sensitivity KRAS mutation testing in metastatic colorectal cancer treated with anti-EGFR antibody therapy.

Oncology 2012 28;82(5):298-304. Epub 2012 Apr 28.

Department of Gastroenterology and Oncology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.

Objective: We compared high-sensitivity KRAS mutation testing with direct sequencing for predicting the efficacy of antiepidermal growth factor receptor antibodies in patients with metastatic colorectal cancer (mCRC).

Methods: We analyzed the KRAS status in 61 tumors from cetuximab-treated mCRC patients by both direct sequencing and a high-sensitivity method: 2-step PCR restriction fragmentation length polymorphism (RFLP). Therapeutic effects in each mutational status were evaluated.

Results: The incidences of KRAS mutations determined by direct sequencing and 2-step PCR RFLP were 34.4 and 52.5%, respectively (p = 0.02). Patients were categorized into 3 groups [W/W, wild-type by both methods (n = 29); W/M, wild-type by direct sequencing, detected mutation by 2-step PCR RFLP (n = 11); M/M, mutant-type by both methods (n = 21)]. The response rate for cetuximab in the W/M group (0%) was the same as that in the M/M group, and was significantly lower than in the W/W group (41.4%) (p < 0.001). Progression-free survival in the W/M group (11.0 weeks) was similar to that in the M/M group (8.0 weeks), and was significantly shorter than in the W/W group (18.0 weeks) (p < 0.002).

Conclusion: High-sensitivity KRAS mutation testing is useful for selecting true responders to cetuximab.

Download full-text PDF

Source
https://www.karger.com/Article/FullText/336792
Publisher Site
http://dx.doi.org/10.1159/000336792DOI Listing
July 2012
9 Reads

Publication Analysis

Top Keywords

direct sequencing
16
kras mutation
12
mutation testing
12
high-sensitivity kras
12
2-step pcr
12
m/m group
8
metastatic colorectal
8
w/m group
8
colorectal cancer
8
w/w group
8
pcr rflp
8
group
6
kras
5
survival w/m
4
fragmentation length
4
length polymorphism
4
cetuximab-treated mcrc
4
restriction fragmentation
4
wild-type direct
4
rflp therapeutic
4

References

(Supplied by CrossRef)

Jonker DJ et al.
N Engl J Med 2007

Sobrero AF et al.
J Clin Oncol 2008

Van Cutsem E et al.
N Engl J Med 2009

Karapetis CS et al.
N Engl J Med 2008

Amado RG et al.
J Clin Oncol 2008

Douillard JY et al.
J Clin Oncol 2010

Peeters M et al.
J Clin Oncol 2010

Malumbres M et al.
Nat Rev Cancer 2003

Andreyev HJ et al.
J Natl Cancer Inst 1998

Jimeno A et al.
J Clin Oncol 2009

Eisenhauer EA et al.
Eur J Cancer 2009

Similar Publications