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首页> 外文期刊>British Journal of Cancer >Correlation of extended RAS and PIK3CA gene mutation status with outcomes from the phase III AGITG MAX STUDY involving capecitabine alone or in combination with bevacizumab plus or minus mitomycin C in advanced colorectal cancer
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Correlation of extended RAS and PIK3CA gene mutation status with outcomes from the phase III AGITG MAX STUDY involving capecitabine alone or in combination with bevacizumab plus or minus mitomycin C in advanced colorectal cancer

机译：扩展 RAS 和 PIK3CA 基因突变状态与III期AGITG MAX研究结果的相关性，AGITG MAX研究仅涉及卡培他滨或与贝伐单抗加或减丝裂霉素C联合治疗晚期大肠癌

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Background: Mutations affecting RAS genes are now established predictive markers of nonresponse to anti-EGFR antibodies in advanced CRC. This analysis assessed the prognostic and predictive impact of extended RAS and PIK3CA gene mutation status in patients receiving capecitabine plus or minus bevacizumab (±mitomycin C) in the randomised phase III MAX study. Methods: DNA was extracted from archival macrodissected formalin-fixed paraffin-embedded tumour tissue. Mutation status was determined using pyrosequencing, confirmed with Sanger sequencing (for equivocal RAS ) and correlated with efficacy outcomes. Predictive analyses were undertaken using a test for interaction involving both C vs CB+CBM. Results: Of the available 280 of the 471 (59.4%) patients, mutations in KRAS exons 2, 3 and 4 and NRAS 2, 3 and 4 were as follows: 32%, 2.9%, 2.2%, 1.4%, 0.7% and 0% (total RAS MT 39%). The PIK3CA MT rate was 7.5% exon 9 and 3.6% exon 20. Extended RAS gene mutation status (WT vs MT) had no prognostic impact for PFS (HR 0.91 (0.71–1.17)) or OS (HR 0.95 (0.71–1.25)). The RAS gene mutation status was not predictive of the effectiveness of bevacizumab for PFS (HR 0.56 (0.37–0.85) for RAS MT and HR 0.69 (0.5–0.97) for RAS WT; P for interaction 0.50). The PIK3CA mutation was neither predictive for bevacizumab effect nor prognostic. Conclusion: Of KRAS exon 2 WT patients, 10% had additional RAS mutations. Neither all RAS gene mutation status nor PIK3CA mutation status was prognostic for PFS or OS, or predictive of bevacizumab outcome in patients with advanced CRC.
机译：背景：影响RAS基因的突变现已确立为晚期CRC中对抗EGFR抗体无反应的预测标记。这项分析在随机III期MAX研究中评估了扩展的RAS和PIK3CA基因突变状态对接受卡培他滨加或减贝伐单抗（±丝裂霉素C）的患者的预后和预测影响。方法：从存档的解剖性福尔马林固定石蜡包埋的肿瘤组织中提取DNA。使用焦磷酸测序确定突变状态，并通过Sanger测序（对于模棱两可的RAS）进行确认，并与疗效结果相关。使用涉及C与CB + CBM的相互作用测试对结果进行了预测分析。结果：在471位患者中的280位（59.4％）患者中，KRAS外显子2、3、4和NRAS 2、3和4的突变如下：32％，2.9％，2.2％，1.4％，0.7％和0％（总RAS MT占39％）。 PIK3CA MT的外显子9率为7.5％，外显子20的3.6％。扩展的RAS基因突变状态（WT vs MT）对PFS（HR 0.91（0.71-1.17））或OS（HR 0.95（0.71-1.25））没有预后影响。 ）。 RAS基因突变状态不能预测贝伐单抗对PFS的有效性（RAS MT HR 0.56（0.37–0.85），RAS WT HR 0.69（0.5–0.97）; P相互作用0.50）。 PIK3CA突变既不能预测贝伐单抗的作用，也不能预后。结论：在KRAS外显子2 WT患者中，有10％的患者还有RAS突变。所有RAS基因突变状态和PIK3CA突变状态都不能预后PFS或OS，也不能预测贝伐单抗在晚期CRC患者中的预后。

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