| General information |
| Database: | DB00999 |
| Objective: | RAS mutations predict resistance to antiepidermal growthfactor receptor (EGFR) monoclonal antibodies in metastatic colorectal cancer. they analysed RAS mutations in 30 nonmetastatic rectal cancer patients treated with or without cetuximab within the 31 EXPERTC trial |
| Authors: | Sclafani F, et al |
| Title: | RAS mutations and cetuximab in locally advanced rectal cancer: results of the EXPERTC trial. |
| Journal: | Eur J Cancer. |
| Year: | 2014 |
| PMID: | 24582914 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced rectal cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | results of the EXPERTC trial |
| Key Patients Feature: | patients with tumours available for analysis were KRAS/BRAF wildtype |
| Biomarker: | RAS mutations |
| Biomark Analysis: | in RAS wildtype population, after a median followup of 63.8months, in line with the initial analysis, the addition of cetuximab was associated with numerically higher, but not statistically significant, rates of complete response (15.8% versus 7.5%, p=0.31), 5year progression free survival (75.5% versus 67.5%, hazard ratio (HR) 0.61, p=0.25) and 5year overall survival (83.8% versus 70%, HR 0.54, p=0.20). |
| Control Group Info: | single arm |
| Treatment Info: | pts were randomly assigned to capecitabine plus oxaliplatin (CAPOX) follotheyd by chemoradiotherapy, surgery and adjuvant CAPOX or the same regimen plus cetuximab (CAPOXC). Of these, four had a mutation of NRAS exon 3, and 84 were retrospectively analysed for additional KRAS (exon 4) and NRAS (exons 2/4) mutations by using bidirectional Sanger sequencing |
| Primary End Point: | The effect of cetuximab on study endpoints in the RAS wildtype population was analysed. |
| Secondary End Point: | NA |
| Patients Number: | 149 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 15.8% versus 7.5% |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 5year progression free survival: 75.5% versus 67.5% |
| Median OS A vs. C: | 5year overall survival: 83.8% versus 70% |
| Adverse Event(agent arm): | NA |
| Conclusions: | RAS mutations beyond KRAS exon 2 and 3 were identified in 17% of locally advanced rectal cancer patients. Given the small sample size, no definitive conclusions on the effect of additional RAS mutations on cetuximab treatment in this setting can be drawn and further investigation of RAS in larger studies is warranted. |