TY - JOUR
T1 - Primary tumor location predicts poor clinical outcome with cetuximab in RAS wild-type metastatic colorectal cancer
AU - Kim, Dalyong
AU - Kim, Sun Young
AU - Lee, Ji Sung
AU - Hong, Yong Sang
AU - Kim, Jeong Eun
AU - Kim, Kyu pyo
AU - Kim, Jihun
AU - Jang, Se Jin
AU - Yoon, Young Kwang
AU - Kim, Tae Won
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/11/23
Y1 - 2017/11/23
N2 - Background: In metastatic colorectal cancer, the location of the primary tumor has been suggested to have biological significance. In this study, we investigated whether primary tumor location affects cetuximab efficacy in patients with RAS wild-type metastatic colorectal cancer. Methods: Genotyping by the SequenomMassARRAY technology platform (OncoMap) targeting KRAS, NRAS, PIK3CA, and BRAF was performed in tumors from 307 patients who had been given cetuximab as salvage treatment. Tumors with mutated RAS (KRAS or NRAS; n = 127) and those with multiple primary location (n = 10) were excluded. Right colon cancer was defined as a tumor located in the proximal part to splenic flexure. Results: A total of 170 patients were included in the study (right versus left, 23 and 147, respectively). Patients with right colon cancer showed more mutated BRAF (39.1% vs. 5.4%), mutated PIK3CA (13% vs. 1.4%), poorly differentiated tumor (17.4% vs. 3.4%), and peritoneal involvement (26.1% vs. 8.8%) than those with left colon and rectal cancer. Right colon cancer showed poorer progression-free survival (2.0 vs.5.0 months, P = 0.002) and overall survival (4.1 months and 13.0 months, P < 0.001) than the left colon and rectal cancer. By multivariable analysis, BRAF mutation, right colon primary, poorly differentiated histology, and peritoneal involvement were associated with risk of death. Conclusions: In RAS wild-type colon cancer treated with cetuximab as salvage treatment, right colon primary was associated with poorer survival outcomes than left colon and rectal cancer.
AB - Background: In metastatic colorectal cancer, the location of the primary tumor has been suggested to have biological significance. In this study, we investigated whether primary tumor location affects cetuximab efficacy in patients with RAS wild-type metastatic colorectal cancer. Methods: Genotyping by the SequenomMassARRAY technology platform (OncoMap) targeting KRAS, NRAS, PIK3CA, and BRAF was performed in tumors from 307 patients who had been given cetuximab as salvage treatment. Tumors with mutated RAS (KRAS or NRAS; n = 127) and those with multiple primary location (n = 10) were excluded. Right colon cancer was defined as a tumor located in the proximal part to splenic flexure. Results: A total of 170 patients were included in the study (right versus left, 23 and 147, respectively). Patients with right colon cancer showed more mutated BRAF (39.1% vs. 5.4%), mutated PIK3CA (13% vs. 1.4%), poorly differentiated tumor (17.4% vs. 3.4%), and peritoneal involvement (26.1% vs. 8.8%) than those with left colon and rectal cancer. Right colon cancer showed poorer progression-free survival (2.0 vs.5.0 months, P = 0.002) and overall survival (4.1 months and 13.0 months, P < 0.001) than the left colon and rectal cancer. By multivariable analysis, BRAF mutation, right colon primary, poorly differentiated histology, and peritoneal involvement were associated with risk of death. Conclusions: In RAS wild-type colon cancer treated with cetuximab as salvage treatment, right colon primary was associated with poorer survival outcomes than left colon and rectal cancer.
KW - Cetuximab
KW - EGFR
KW - Metastatic colorectal cancer
KW - Primary tumor location
KW - RAS wild-type
UR - http://www.scopus.com/inward/record.url?scp=85035194470&partnerID=8YFLogxK
U2 - 10.1186/s12876-017-0694-6
DO - 10.1186/s12876-017-0694-6
M3 - Article
C2 - 29169325
AN - SCOPUS:85035194470
SN - 1471-230X
VL - 17
JO - BMC Gastroenterology
JF - BMC Gastroenterology
IS - 1
M1 - 121
ER -
