Retrospective study of RAS/PIK3CA/BRAF tumor mutations as predictors of response to first-line chemotherapy with bevacizumab in metastatic colorectal cancer patients.
Retrospective study of RAS/PIK3CA/BRAF tumor mutations as predictors of response to first-line chemotherapy with bevacizumab in metastatic colorectal cancer patients.
复制标题
RAS/PIK3CA/BRAF肿瘤突变的回顾性研究是转移性结直肠癌患者对一线化学疗法反应的预测指标。
DOI：
10.1186/s12885-016-2994-6
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发表时间：
2017-01-09
期刊：
影响因子：
3.8
通讯作者：
Yamaguchi K
中科院分区：
文献类型：
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作者：
Nakayama I;Shinozaki E;Matsushima T;Wakatsuki T;Ogura M;Ichimura T;Ozaka M;Takahari D;Suenaga M;Chin K;Mizunuma N;Yamaguchi K
在 FIRE-3 和 PRIME 研究中对微小 RAS 突变（KRAS 外显子 3、4/NRAS）进行分析后，扩大了 RAS 突变范围，被确立为抗 EGFR 抗体治疗效果的阴性预测标记。 BRAF和PIK3CA突变可能是抗EGFR靶向治疗的候选生物标志物。然而，RAS/PIK3CA/BRAF肿瘤突变是否可以预测贝伐单抗在转移性结直肠癌中的疗效仍不清楚。我们评估了根据 RAS/PIK3CA/BRAF 突变状态进行的选择对于接受贝伐单抗作为转移性结直肠癌一线治疗的患者是否有益。在使用多重试剂盒 (Luminex®) 对 1001 名连续结直肠癌患者进行 RAS、PIK3CA 和 BRAF 肿瘤突变检查中，我们研究了 90 名接受贝伐单抗联合化疗作为转移性结直肠癌一线治疗的患者。根据突变状态评估客观缓解率（ORR）和无进展生存期（PFS）。与仅 KRAS 外显子 2 为野生型的肿瘤患者 (54.8%) 相比，野生型肿瘤患者的 ORR 较高 (64.3%)，并且仅考虑 KRAS 外显子 2 突变 (6.8%) 而不是 RAS/PIK3CA/BRAF 突变 (18.4%) 时，野生型肿瘤患者和突变型肿瘤患者之间的 ORR 差异更大。所有野生型肿瘤和携带任何突变的肿瘤之间的 ORR 或 PFS 没有统计学上的显着差异。多变量分析显示，肝转移以及RAS和BRAF突变是贝伐珠单抗一线治疗后疾病进展的独立负面因素。根据 RAS/PIK3CA/BRAF 突变选择患者可以帮助选择对贝伐珠单抗治疗有更好反应的患者。我们发现限制贝伐单抗联合治疗对于患有 EGFR 野生型肿瘤的转移性结直肠癌患者没有临床益处。本文的在线版本 (doi:10.1186/s12885-016-2994-6) 包含补充材料，可供授权用户使用。
After analysis of minor RAS mutations (KRAS exon 3, 4/NRAS) in the FIRE-3 and PRIME studies, an expanded range of RAS mutations were established as a negative predictive marker for the efficacy of anti-EGFR antibody treatment. BRAF and PIK3CA mutations may be candidate biomarkers for anti-EGFR targeted therapies. However, it remains unknown whether RAS/PIK3CA/BRAF tumor mutations can predict the efficacy of bevacizumab in metastatic colorectal cancer. We assessed whether selection according to RAS/PIK3CA/BRAF mutational status could be beneficial for patients treated with bevacizumab as first-line treatment for metastatic colorectal cancer. Of the 1001 consecutive colorectal cancer patients examined for RAS, PIK3CA, and BRAF tumor mutations using a multiplex kit (Luminex®), we studied 90 patients who received combination chemotherapy with bevacizumab as first-line treatment for metastatic colorectal cancer. The objective response rate (ORR) and progression-free survival (PFS) were evaluated according to mutational status. The ORR was higher among patients with wild-type tumors (64.3%) compared to those with tumors that were only wild type with respect to KRAS exon 2 (54.8%), and the differences in ORR between patients with wild-type and mutant-type tumors were greater when considering only KRAS exon 2 mutations (6.8%) rather than RAS/PIK3CA/BRAF mutations (18.4%). There were no statistically significant differences in ORR or PFS between all wild-type tumors and tumors carrying any of the mutations. Multivariate analysis revealed that liver metastasis and RAS and BRAF mutations were independent negative factors for disease progression after first-line treatment with bevacizumab. Patient selection according to RAS/PIK3CA/BRAF mutations could help select patients who will achieve a better response to bevacizumab treatment. We found no clinical benefit of restricting combination therapy with bevacizumab for metastatic colorectal cancer patients with EGFR-wild type tumors. The online version of this article (doi:10.1186/s12885-016-2994-6) contains supplementary material, which is available to authorized users.