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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2017.1
- 수록면
- 37 - 43 (7page)
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Purpose Cetuximab demonstrates improved efficacy outcomes in patients with metastatic colorectal cancer (mCRC) harboring wild-type KRAS exon 2. Resistance to cetuximab is mediated by activating less frequent mutations in the RAS genes beyond KRAS exon 2. We performed extended RASmutational analysis using a high -throughput genotyping platform (OncoMap) and evaluated extended RAS analysis for predicting cetuximab efficacy in patients harboring wild-type KRAS exon 2 tumors following Sanger sequencing.
Materials and Methods Extended RAS analysis was performed on 227 wild-type KRAS exon 2 mCRC patients who received cetuximab as salvage treatment using OncoMap ver. 4.0. Targeted genes included exon 2, exon 3, and exon 4, both in KRAS and NRAS, and included BRAF exon 15. We assessed efficacy by the new RAS mutation status.
Results The OncoMap detected 57 additional mutations (25.1%): 25 (11%) in KRAS exon 2 and 32 (14.1%) beyond KRAS exon 2. Survival differences were observed after dividing patients into the wild-type RAS group (n=170) and mutant RAS group (n=57) using OncoMap.
Progression-free survival was 4.8 months versus 1.8 months (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.32 to 0.61), and overall survival was 11.9 months versus 8.4 months (HR, 0.65; 95% CI, 0.47 to 0.88).
Conclusion Sanger sequencing is not sufficient for selecting candidates for cetuximab treatment. High - throughput extended RAS genotyping is a feasible approach for this purpose and identifies patients who might benefit from cetuximab treatment.
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참고문헌 (19)
참고문헌 신청
Atreya CE / 2015 / Expanded RAS : refining the patient population / J Clin Oncol 33 : 682 ~ 685
Bokemeyer C / 2012 / Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer : pooled analysis of the CRYSTAL and OPUS
Bokemeyer C / 2015 / FOLFOX4 plus cetuximab treatment and RAS mutations in colorectal cancer / Eur J Cancer 51 : 1243 ~ 1252
Ciardiello F / 2011 / Uptake of KRAS mutation testing in patients with metastatic colorectal cancer in Europe, Latin America and Asia / Target Oncol 6 : 133 ~ 145
Di Fiore F / 2007 / Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by cetuximab plus chemotherapy / Br J Cancer 96 : 1166 ~ 1169
Bokemeyer C / 2012 / Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer : pooled analysis of the CRYSTAL and OPUS
Bokemeyer C / 2015 / FOLFOX4 plus cetuximab treatment and RAS mutations in colorectal cancer / Eur J Cancer 51 : 1243 ~ 1252
Ciardiello F / 2011 / Uptake of KRAS mutation testing in patients with metastatic colorectal cancer in Europe, Latin America and Asia / Target Oncol 6 : 133 ~ 145
Di Fiore F / 2007 / Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by cetuximab plus chemotherapy / Br J Cancer 96 : 1166 ~ 1169
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