Background: Treatment with antiepidermal growth factor receptor (anti-EGFR) monoclonal antibodies has been restricted to metastatic colorectal cancer (mCRC) patients with RAS wild-type tumors VSports手机版. Next-generation sequencing (NGS) allows the assessment in a single analysis of a large number of gene alterations and might provide important predictive and prognostic information. .

Patients and methods: In the CAPRI-GOIM trial, 340 KRAS exon 2 wild-type mCRC patients received first-line FOLFIRI plus cetuximab. Tumor samples (182/340, 53. 5%) were assessed by NGS to search for mutations in 22 genes involved in colon cancer V体育安卓版. .

Results: Objective responses in the NGS cohort were observed in 104/182 patients [overall response rate (ORR) 57. 1%; 95% confidence interval (95% CI) 52% to 66. 4%] with a median progression-free survival (mPFS) of 9. 8 (95% CI 8. 7-11. 5) months. NGS analysis was successfully completed in all 182 samples. One or more gene mutations (up to five) were detected in 124/182 (68. 1%) tumors within 14/22 genes for a total of 206 mutations. KRAS exon 2 mutations were identified in 29/182 (15. 9%) samples, defined as wild type by local laboratory assessment. Frequently mutated genes were: TP53 (39. 6%), KRAS exons 3/4 (8 V体育ios版. 8%), NRAS exons 2/3 (7. 1%), PIK3CA exons 9/20 (13. 2%), BRAF (8. 2%). FOLFIRI plus cetuximab treatment determined ORR of 62. 0% (95% CI 55. 5% to 74. 6%) with mPFS of 11. 1 (95% CI 9. 2-12. 8) months in patients with KRAS and NRAS wild-type tumors. Conversely, ORR was 46. 6% (95% CI 39. 9-57. 5%) with mPFS of 8. 9 (95% CI 7. 4-9. 6) months in patients with KRAS or NRAS mutations. Similarly, the subgroup of patients carrying KRAS, NRAS, BRAF, or PIK3CA mutations showed a worse outcome, although this might be due to a prognostic effect. .

Conclusions: This study demonstrates that NGS analysis in mCRC is feasible, reveals high level of intra and intertumor heterogeneity, and identifies patients that might benefit of FOLFIRI plus cetuximab treatment VSports最新版本. .