Worse prognosis of KRAS c.35 G > A mutant metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx)

被引：24

作者：

Bruera, Gemma ^{[1
,2
]}

Cannita, Katia ^{[1
]}

Di Giacomo, Daniela ^{[2
]}

Lamy, Aude ^{[3
]}

Frebourg, Thierry ^{[4
]}

Sabourin, Jean Christophe ^{[5
]}

Tosi, Mario ^{[4
]}

Alesse, Edoardo ^{[2
]}

Ficorella, Corrado ^{[1
,2
]}

Ricevuto, Enrico ^{[1
,2
]}

机构：

[1] Univ Aquila, S Salvatore Hosp, I-67100 Laquila, Italy

[2] Univ Aquila, Dept Biotechnol & Appl Clin Sci, I-67100 Laquila, Italy

[3] Univ Hosp, Lab Tumor Genet, F-76031 Rouen, France

[4] Univ Rouen, INSERM U614, F-76183 Rouen, France

[5] Rouen Univ Hosp, Dept Pathol, INSERM U614, F-76031 Rouen, France

来源：

BMC MEDICINE | 2013年 / 11卷

关键词：

KRAS mutation; Kras c.35 G > A mutation; triplet chemotherapy plus bevacizumab; metastatic colorectal cancer; FIr-B/FOx; KIRSTEN RAS MUTATIONS; 1ST-LINE TREATMENT; K-RAS; P.G13D MUTATION; CODON; 12; CETUXIMAB; ASSOCIATION; OXALIPLATIN; LEUCOVORIN; IRINOTECAN;

D O I：

10.1186/1741-7015-11-59

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Prognosis of KRAS wild-type and mutant metastatic colorectal cancer (MCRC) patients (pts) treated with bevacizumab (BEV)-containing chemotherapy is not significantly different. Since specific KRAS mutations confer different aggressive behaviors, the prognostic role of prevalent KRAS mutations was retrospectively evaluated in MCRC pts treated with first line FIr-B/FOx, associating BEV to triplet chemotherapy. Methods: Tumor samples were screened for KRAS codon 12, 13 and BRAF V600E mutations by SNaPshot and/or direct sequencing. MCRC pts <75-years-old were consecutively treated with FIr-B/FOx: weekly 12 hour-timed-flat-infusion/5-fluorouracil (900 mg/m(2) on days 1,2, 8, 9, 15, 16,22, 23), irinotecan plus BEV (160 mg/m(2) and 5 mg/kg, respectively, on days 1,15); and oxaliplatin (80 mg/m(2), on days 8,22). Pts were classified as liver-limited (L-L) and other/multiple metastatic (O/MM). Progression-free survival (PFS) and overall survival (OS) were compared using the log-rank test. Results: Fifty-nine pts were evaluated at a median follow-up of 21.5 months. KRAS mutant pts: c.35 G > A, 15 (25.4%); c.35 G > T, 7 (11.8%); c.38 G > A, 3 (5%); other, 3 (5%). KRAS wild-type, 31 pts (52.7%). The objective response rate (ORR), PFS and OS were, respectively: c.35 G > A mutant, 71%, 9 months, 14 months; other than c.35 G > A mutants, 61%, 12 months, 39 months. OS was significantly worse in c.35 G > A pts compared to KRAS wild-type (P = 0.002), KRAS/BRAF wild-type (P = 0.03), other MCRC patients (P = 0.002), other than c.35 G > A (P = 0.05), other codon 12 (P = 0.03) mutant pts. OS was not significantly different compared to c.35 G > T KRAS mutant (P = 0.142). Conclusions: KRAS c.35 G > A mutant status may be significantly associated with a worse prognosis of MCRC pts treated with first line FIr-B/FOx intensive regimen compared to KRAS/BRAF wild type and other than c.35 G > A mutant pts.

引用

页数：10

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Worse prognosis of KRAS c.35 G &gt; A mutant metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx)

Worse prognosis of KRAS c.35 G > A mutant metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx)