| General information |
| Database: | DB00983 |
| Objective: | the phase III CRYSTAL study demonstrated that addition of cetuximab to fluorouracil, leucovorin, and irinotecan (FOLFIRI) significantly improved overall survival, progression free survival, and objective response in the firstline treatment of patients with KRAS codon 12/13 (exon 2) wildtype metastatic colorectal cancer (mCRC). Outcome was reassessed in subgroups defined by extended RAS mutation testing. |
| Authors: | Van Cutsem E, et al |
| Title: | Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. |
| Journal: | J Clin Oncol. |
| Year: | 2015 |
| PMID: | 25605843 |
| Trial Design |
| Clinical Trial Id: | NCT00154102 |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | colorectal cancer with RAS mutations |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Fluorouracil, leucovorin, + irinotecan + cetuximab |
| Study Type: | subanalyses of the phase III CRYSTAL study |
| Key Patients Feature: | Existing DNA samples from KRAS exon 2 wildtype tumors from CRYSTAL study patients |
| Biomarker: | RAS mutation |
| Biomark Analysis: | In patients with other RAS tumor mutations, no difference in efficacy outcomes between treatment groups was seen. The safety profile in RAS subgroups was similar and in line with expectations. |
| Control Group Info: | single arm |
| Treatment Info: | pts were reanalyzed for other RAS mutations in four additional KRAS codons (exons 3 and 4) and six NRAS codons (exons 2, 3, and 4) using beads, emulsion, amplification, and magnetics technology. No tissue microdissection was performed |
| Primary End Point: | extended RAS mutation testing |
| Secondary End Point: | NA |
| Patients Number: | 430 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The overall incidence of adverse events according to treatment group was broadly similar across the KRAS and RAS subgroups (Table 3). In addition, the incidence of commonly reported adverse events in each treatment group was also generally similar across these populations and in line with expectations. |
| Conclusions: | In the firstline treatment of mCRC, patients with RAS wildtype tumors derived a significant benefit from the addition of cetuximab to FOLFIRI; patients with RAS tumor mutations did not. Molecular testing of tumors for all activating RAS mutations is essential before considering antiepidermal growth factor receptor therapy, thereby allowing the further tailoring of cetuximab administration to maximize patient benefit. |