Using next-generation sequencing technology to evaluate biomarkers associated with anti-EGFR efficacy in metastatic colorectal cancer / 中国肿瘤临床

ABSTRACT

Objective:To explore genes associated with sensitivity to anti-EGFR therapy. Methods:From March 2012 to August 2013, 31 metastatic colorectal cancer patients in Peking University Cancer Hospital&Institute were treated with anti-EGFR mono-therapy. A total of 21 genes associated with oncogenesis, metastasis, and EGFR signaling pathway were profiled in these 31 patients by using tar-geted next-generation sequencing technology. Results:A total of 31 patients with Kras exon 2 wild-type received anti-EGFR therapy as third-line treatment. Among these patients, the median progression-free survival (PFS) was 89 days, overall survival was 311 days, and objective response rate was 16.1%. Five cases harbored Kras exons 3/4 or Nras exons 2/3 mutations. These five Ras mutation patients showed disease progression during the first evaluation with 31-day PFS. One PIK3CA mutation case exhibited disease progression dur-ing the first evaluation (PFS 35 days), and one case showed mTOR mutation with 91-day PFS. The PFS of two cases with SMAD4 muta-tion were 58 and 59 days, whereas that of the case containing FBXW7 mutation was 93 days. Among the 26 Ras wild-type patients, MLL3, TP53, and APC were the three genes with the highest mutation frequencies of 92.3%(24/26), 53.8%(14/26), and 42.3%(11/26), respectively. Conclusion:Extended Ras analysis (including Kras and Nras exons 2/3/4) is recommended for patients who are candi-dates for anti-EGFR therapy. Mutations in the downstream effectors of the EGFR signaling pathway, such as PI3KCA and mTOR, may al-so have a predictive role in anti-EGFR therapy. Mutations beyond the EGFR pathway such as FBXW7 and SMAD4 may be associated with anti-EGFR efficacy and deserve further attention.