CRYSTAL study design and post hoc analyses1-3,5
CRYSTAL study design
CRYSTAL was a phase III, open-label, randomized, multicenter study (N=1217) conducted outside the United States that used a cetuximab product as the clinical trial material.1
- ERBITUX provides approximately 22% higher exposure relative to the cetuximab used in this study; these pharmacokinetic data, together with the results of the CRYSTAL study and other clinical trial data, establish the efficacy of ERBITUX at the recommended dose in combination with FOLFIRI for first-line treatment of KRAS exon 2 wild-type, EGFR-expressing mCRC
- Patients were randomized (1:1) to receive either cetuximab in combination with FOLFIRIǁ (n=608) (the CRYSTAL regimen) or FOLFIRI aloneǁ (n=609) as first-line treatment until disease progression or unacceptable toxicity occurred
- The main outcome measure of this trial was PFS assessed by an IRC. Other outcome measures were OS and ORR
KRAS post hoc analysis
- In the KRAS wild-type subpopulation, patients received a median of 24 infusions of cetuximab (range 1 to 224)
- KRAS mutation status was available for 89% of the patients (n=1079): 63% of patients had KRAS wild-type tumors (n=676: CRYSTAL regimen, n=320; FOLFIRI alone, n=356) and 37% of patients had KRAS-mutant tumors (n=403)
Extended RAS post hoc analysis
In this post hoc analysis of the CRYSTAL study, patient tumor samples with predefined RAS mutations other than KRAS exon 2 were evaluated. In addition, treatment effect in patients with any evaluable RAS wild-type tumor sample was also evaluated.3
- Among patients with KRAS exon 2 wild-type tumors (n=666); 65% (n=430) were evaluable for RAS mutation status; of those, 85% (n=367) had RAS wild-type tumors
- A post hoc analysis of efficacy data was performed on patient subgroups defined by RAS mutation status (RAS wild-type subpopulation: CRYSTAL regimen, n=178; FOLFIRI alone, n=189)
ǁPatients who received cetuximab with FOLFIRI were given an initial intravenous (IV) infusion of cetuximab 400 mg/m2 followed by weekly infusions of 250 mg/m2 administered 1 hour prior to chemotherapy. For all patients, the FOLFIRI regimen included 14-day cycles of irinotecan (180 mg/m2 IV on day 1), folinic acid (400 mg/m2 [racemic] or 200 mg/m2 [L-form] IV on day 1), and fluorouracil (400 mg/m2 bolus on day 1 followed by 2400 mg/m2 as a 46-hour continuous infusion).1
Primary tumor location RAS post hoc analysis
In this post hoc analysis of the CRYSTAL study, patients with RAS wild-type mCRC were evaluated based on primary tumor location.5
- Among patients with RAS wild-type tumors (n=367), 99% (n=364) were evaluable for primary tumor location; of those, 76% (n=280) had left-sided tumors and 23% (n=84) had right-sided tumors. Patients with transverse colon tumors were included in the right-sided analysis
- A post hoc analysis of efficacy data was performed on patient subgroups defined by treatment arm followed by primary tumor location:
- Left-sided tumor subpopulation: CRYSTAL regimen (with a cetuximab product), n=142; FOLFIRI alone, n=138
- Right-sided tumor subpopulation: CRYSTAL regimen (with a cetuximab product), n=33; FOLFIRI alone, n=51