KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer

被引：462

作者：

Loupakis, F. ^{[1
,2
]}

Ruzzo, A. ^{[3
]}

Cremolini, C. ^{[1
,2
]}

Vincenzi, B. ^{[4
]}

Salvatore, L. ^{[1
,2
]}

Santini, D. ^{[4
]}

Masi, G. ^{[1
,2
]}

Stasi, I. ^{[1
,2
]}

Canestrari, E. ^{[3
]}

Rulli, E. ^{[5
]}

Floriani, I. ^{[5
]}

Bencardino, K. ^{[6
]}

Galluccio, N. ^{[3
]}

Catalano, V. ^{[7
]}

Tonini, G.

Magnani, M. ^{[3
]}

Fontanini, G. ^{[8
]}

Basolo, F. ^{[8
]}

Falcone, A. ^{[1
,2
]}

Graziano, F. ^{[7
]}

机构：

[1] Univ Pisana, Azienda Osped, Unit Med Oncol 2, Ist Toscano Tumori, I-56126 Pisa, Italy

[2] Univ Pisa, Dept Oncol Transplantes & New Technol Med, I-56126 Pisa, Italy

[3] Univ Urbino, Sect Biochem & Mol Biol G Fomaini, Dept Biomol Sci, I-61029 Urbino, Italy

[4] Med Oncol Unit, I-00128 Rome, Italy

[5] Mario Negri Inst Pharmacol Res, I-20156 Milan, Italy

[6] Ist Sci San Raffaele, Med Oncol Unit, I-20132 Milan, Italy

[7] Hosp Pesaro, Med Oncol Unit, I-61100 Pesaro, Italy

[8] Univ Pisa, Div Pathol, Dept Surg, Ist Toscano Tumori, Pisa, Italy

来源：

BRITISH JOURNAL OF CANCER | 2009年 / 101卷 / 04期

关键词：

colorectal cancer; cetuximab; KRAS; BRAF; K-RAS MUTATIONS; CHEMOTHERAPY; PANITUMUMAB; BEVACIZUMAB; EXPRESSION; MECHANISM; CARCINOMA; THERAPY; PATHWAY; BENEFIT;

D O I：

10.1038/sj.bjc.6605177

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Assessing KRAS codons 61/146 and BRAF V600E mutations might help optimising the selection of the candidate patients to receive anti-EGFR moAbs. British Journal of Cancer (2009) 101, 715-721. doi: 10.1038/sj.bjc.6605177 www.bjcancer.com Published online 14 July 2009 (C) 2009 Cancer Research UK

引用

页码：715 / 721

页数：7

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