KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer.
KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer.
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KRAS密码子61、146和BRAF突变预测KRAS密码子12和13野生型转移性结直肠癌中对西妥昔单抗和伊立替康的抗性。
DOI：
10.1038/sj.bjc.6605177
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发表时间：
2009-08-18
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
KRAS密码子12和13突变预测转移性结直肠癌对抗EGFR单克隆抗体（moAb）的耐药性。此外，BRAF V600 E突变与耐药性相关。其他KRAS突变在CRC中描述。我们研究了KRAS密码子61和146以及BRAF V600 E突变在预测KRAS密码子12和13野生型患者对西妥昔单抗联合伊立替康耐药的队列中的作用。在87例KRAS密码子12和13例野生型患者中，分别有7例和1例KRAS密码子61和146突变。突变型患者无应答，而野生型患者中有22例应答（P=0.096）。11例患者不可评价。KRAS突变与较短的无进展生存期相关（PFS，HR：0.46，P=0.028）。13例BRAF突变患者无应答，而74例BRAF野生型患者中有24例应答（P=0.016）。BRAF突变与PFS缩短趋势相关（HR：0.59，P=0.073）。在BRAF野生型患者亚组中，KRAS密码子61/146突变决定了较低的缓解率（0 vs 37%，P=0.047）和较差的PFS（HR：0.45，P=0.023）。与KRAS和BRAF野生型患者相比，携带KRAS或BRAF突变的患者的缓解率（0 vs 37%，P=0.0005）和PFS（HR：0.51，P=0.006）较差。评估KRAS密码子61/146和BRAF V600 E突变可能有助于优化候选患者的选择以接受抗EGFR moAb。
KRAS codons 12 and 13 mutations predict resistance to anti-EGFR monoclonal antibodies (moAbs) in metastatic colorectal cancer. Also, BRAF V600E mutation has been associated with resistance. Additional KRAS mutations are described in CRC. We investigated the role of KRAS codons 61 and 146 and BRAF V600E mutations in predicting resistance to cetuximab plus irinotecan in a cohort of KRAS codons 12 and 13 wild-type patients. Among 87 KRAS codons 12 and 13 wild-type patients, KRAS codons 61 and 146 were mutated in 7 and 1 case, respectively. None of mutated patients responded vs 22 of 68 wild type (P=0.096). Eleven patients were not evaluable. KRAS mutations were associated with shorter progression-free survival (PFS, HR: 0.46, P=0.028). None of 13 BRAF-mutated patients responded vs 24 of 74 BRAF wild type (P=0.016). BRAF mutation was associated with a trend towards shorter PFS (HR: 0.59, P=0.073). In the subgroup of BRAF wild-type patients, KRAS codons 61/146 mutations determined a lower response rate (0 vs 37%, P=0.047) and worse PFS (HR: 0.45, P=0.023). Patients bearing KRAS or BRAF mutations had poorer response rate (0 vs 37%, P=0.0005) and PFS (HR: 0.51, P=0.006) compared with KRAS and BRAF wild-type patients. Assessing KRAS codons 61/146 and BRAF V600E mutations might help optimising the selection of the candidate patients to receive anti-EGFR moAbs.
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影响因子：
50.5
作者：
Spindler, K. -L. Garm;Pallisgaard, N.;Jakobsen, A.
通讯作者：
Jakobsen, A.
影响因子：
5.7
作者：
Buhrman, Greg;Wink, Glenna;Mattos, Carla
通讯作者：
Mattos, Carla
影响因子：
45.3
作者：
Khambata-Ford, Shirin;Garrett, Christopher R.;Mauro, David J.
通讯作者：
Mauro, David J.
影响因子：
51.1
作者：
Linardou, Helena;Dahabreh, Issa J.;Murray, Samuel
通讯作者：
Murray, Samuel
影响因子：
45.3
作者：
Hecht, J. Randolph;Mitchell, Edith;Amado, Rafael G.
通讯作者：
Amado, Rafael G.