2015年ASCO年会于5月29日—6月2日在美国芝加哥召开。5月30日下午消化系统（结直肠）肿瘤口头报告专场上，一项来自PETACC8和N0147试验3934例患者的汇总分析显示了，BRAF V600E与KRAS外显子2突变对经辅助FOL**+/-西妥昔单抗治疗，微卫星稳定（MMS），III期结肠癌患者的预测价值。

既往发表的研究因混杂了II期与III期，微卫星不稳定性（MSI）和MSS,结肠癌与直肠癌，治疗方案不固定等情况，BRAF和KRAS基因突变对术后结肠癌患者的预后影响尚存争议。因此，本项研究前瞻性从接受FOL**+/-西妥昔单抗辅助治疗的III结肠癌患者中收集生物标志。

研究方法：

研究人员对肿瘤BRAF V600E和KRAS外显子2基因突变进行分析，仅将MSS患者纳入组。将这些入组患者分为BRAF突变，KRAS突变，和双重野生型（WT）三组。采用一致性结果评估指标，在全组和各亚组中评估预后影响，然后将所有数据汇总。采用分层Cox比例风险模型对基因突变与复发间期（TTR），复发后生存期（SAR），和总生存期（OS）相关性进行分析。多变量模型对治疗和协变量（年龄，性别，肿瘤分级，T/N分期，肿瘤部位，ECOG PS）进行了校正。

研究结果：

一共入组5577例，仅对3934例MSS患者评估BRAF和KRAS基因；其中279例BRAF突变，1450例KRAS突变，以及2205例双重WT.与WT组不同，突变两组的TTR和OS较短，且多因素分析也证实该结果（表）。WT组，KRAS突变组，BRAF突变组的中位SAR分别为2.57,2.09和1.0年，其中KRAS（HR:1.20-95%CI:1.01-1.44,P<0.0001），BRAF突变组（HR:3.01-95%CI:2.32-3.93,P<0.0001）。本项研究中治疗（联合或不联合西妥昔单抗）和KRAS/BRAF双突变的TTR（P值=0.38）和OS（P值=0.16）无明显差异。

结论：

本项研究通过一项大型III期术后结肠癌接受FOL**辅助治疗试验的汇总分析，发现BRAF V600E或KRAS 外显子2,包括密码子12或13突变，是TTR,SAR和OS的***预测因子。在以后的临床试验辅助试验中应将这些突变纳入为重要分层因素。

会议专题》》》2015年ASCO年会专题报道

Prognostic value of BRAF V600E and KRAS exon 2 mutations in microsatellite stable （MSS）， stage III colon cancers （CC） from patients （pts） treated with adjuvant FOL**+/- cetuximab: A pooled **ysis of 3934 pts from the PETACC8 and N0147 trials.（Abstract 3507）Authors:Julien Taieb, Karine Le Malicot,et al.

Session Type:Oral Abstract Session

Background: The prognostic value of BRAF and KRAS mutations in resected CC pts remains controversial due to published studies that include stage II & III, microsatellite instability （MSI） and MSS, colon and rectal tumors, and variable treatment regimens. We examined this question in prospectively collected biospecimens from MSS stage III CC pts receiving adjuvant FOL** +/- cetuximab.

Methods:Tumors were **yzed for BRAF V600E and KRAS exon 2 mutations, only MSS tumors were included. Three groups were defined: BRAF Mutant, KRAS Mutant and double wild-type （WT）。 The **ytic strategy estimated study- and arm-specific prognostic effects to assess homogeneity of results, and then **ysis of pooled data. Associations of mutations with time-to-recurrence （TTR）， survival after relapse （SAR） and overall survival （OS） were **ysed using a stratified Cox proportional hazards model. Multivariate models were adjusted for treatment and covariates （age, sex, tumor grade, T/N stage, tumor location, ECOG PS）。

Results:Of the 5,577 pts enrolled, 3,934 tumors were MSS and evaluable for BRAF and KRAS; 279 pts were BRAF Mutant, 1,450 KRAS Mutant, and 2,205 WT. Both mutations were linked to shorter TTR and OS vs WT, and results were confirmed in multivariate **yses （table）。 Median SAR was 2.57, 2.09 and 1.0 year in WT, KRAS Mutant （HR: 1.20- 95%CI: 1.01-1.44, p < 0.0001） and BRAF mutant （HR: 3.01-95%CI: 2.32-3.93, p < 0.0001）， respectively. No interaction was found between treatment （with or without cetuximab） and KRAS/BRAFmutations for TTR （p = 0.38） or OS （p = 0.16）。

Conclusions:In a large pooled **ysis of pts with resected stage III MSS colon cancers receiving adjuvant FOL**, BRAFV600E or KRAS exon 2 mutations, including codons 12 or 13, are independent predictors of significantly shorter TTR, SAR and OS. Future clinical trials in the adjuvant setting should consider these mutations as important stratification factors.