Cetuximab and Chemotherapy as Initial Treatment for Metastatic Colorectal Cancer
- Study type
- Clinical trial
- Study name
- CRYSTAL
- Phase
- Phase 3
- Design
- Randomised, controlled trial comparing FOLFIRI alone with FOLFIRI plus cetuximab as first-line treatment
- Sample size
- 1198 patients (599 in each group)
- Source
- N Engl J Med · 2009
- Trial registration
- NCT00154102
In plain words
In this study, patients with bowel (colorectal) cancer that had spread to other organs received either FOLFIRI chemotherapy alone or chemotherapy together with the drug cetuximab. Adding cetuximab slightly lowered the risk of the disease getting worse, but overall survival did not differ significantly. This benefit was seen only in patients whose tumour had no mutation in the KRAS gene (wild type), and side effects such as skin reactions and diarrhoea were more common with cetuximab.
Key results
Treatment arms and regimens
Cetuximab IV with an initial dose of 400 mg/m² then 250 mg/m² weekly, one hour before chemotherapy + FOLFIRI in 14-day cycles: irinotecan 180 mg/m² IV day 1, folinic acid 400 mg/m² (racemic) or 200 mg/m² (L-form) IV day 1, fluorouracil 400 mg/m² bolus day 1 followed by 2400 mg/m² as a 46-hour continuous infusion; until disease progression or unacceptable toxicity.
FOLFIRI at the same doses every 14 days, until disease progression or unacceptable toxicity.
Source of the regimen details: FDA label for cetuximab (ERBITUX; Clinical Studies section, CRYSTAL)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with epidermal growth factor receptor (EGFR)-positive colorectal cancer with unresectable metastases.
Endpoints
Primary endpoint: progression-free survival. Assessing the association of tumour KRAS mutation status with clinical response to cetuximab was also an aim of the study. Other endpoints included overall survival and tumour response.
Safety and side effects
Grade 3 or 4 adverse events were more common with cetuximab + FOLFIRI than with FOLFIRI alone: skin reactions (grade 3 only) 19.7% versus 0.2% (P<0.001), infusion-related reactions 2.5% versus 0% (P<0.001) and diarrhoea 15.7% versus 10.5% (P=0.008).
Clinical significance and place in guidelines
This study showed that the benefit of cetuximab in first-line treatment of metastatic colorectal cancer is limited to patients with KRAS wild-type tumours; testing KRAS mutation status before deciding to use this drug is therefore important. The current status of this approach in treatment guidelines should be checked separately, as the abstract gives no information on drug approval or guideline recommendations.
Limitations
Based on the abstract: adding cetuximab did not improve overall survival. The test for interaction with KRAS status was not significant for progression-free survival and overall survival (P=0.07 and P=0.44, respectively), and a significant interaction was seen only for tumour response. Other limitations should be checked in the full text of the paper.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.