KRAS status and efficacy in the first-line treatment of patients with metastatic colorectal cancer treated with FOLFIRI with or without cetuximab: The CRYSTAL experience Eric Van Cutsem* I Lang, G D’Haens, V Moieseyenko, J Zaluski, G Folprecht, S Tejpar, O Kisker, C Stroh, P Rougier *University Hospital Gasthuisberg, Leuven, Belgium
KRAS status and efficacy in the first-line treatment of patients with metastatic colorectal cancer treated with FOLFIRI with or without cetuximab: The CRYSTAL experience. Eric Van Cutsem* - PowerPoint PPT Presentation
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KRAS status and efficacy in the first-line treatment of patients with metastatic colorectal cancer treated with FOLFIRI with or without cetuximab:The CRYSTAL experience
Eric Van Cutsem*
I Lang, G D’Haens, V Moieseyenko, J Zaluski, G Folprecht, S Tejpar, O Kisker, C Stroh, P Rougier*University Hospital Gasthuisberg, Leuven, Belgium
Retrospective studies supporting the correlation between KRAS mutations and lack of response to
EGFR inhibitors in chemorefractory mCRCReference Treatment No. of patients
(wild-type:mutant)Objective response
n (%)
Wild-type mutant
A Lièvre et al, (J Clin Oncol 2008)
Cetuximab ± CT 114 (78:36) 34 (44) 0 (0)
S Benvenuti et al, (Cancer Res 2007)
Panitumumab or cetuximab or Cetuximab + CT
48 (32:16) 10 (31) 1 (6)
W DeRoock, E Van Cutsem S Tejpar (Ann Oncol 2008)
Cetuximab or Cetuximab + irinotecan
113 (67:46) 27 (41) 0 (0)
D Finocchiaro et al, (ASCO Proceedings 2007)
Cetuximab ± CT 81 (49:32) 13 (26) 2 (6)
F Di Fiore et al, (Br J Cancer 2007)
Cetuximab + CT 59 (43:16) 12 (28) 0 (0)
S Khambata-Ford et al, (J Clin Oncol 2007)
Cetuximab 80 (50:30) 5 (10) 0 (0)
RG Amado et al, (J Clin Oncol 2008)
Panitumumab 208 (124:84) 21 (17) 0 (0)
First-line cetuximab + FOLFIRI: Correlation of KRAS status with efficacy
First-line treatment: cetuximab (6 weeks monotherapy), followed by cetuximab + FOLFIRI (n=52)
Cetuximab Cetuximab + FOLFIRI
Outcome Wild-type Mutant Wild-type Mutant
RR (CR+PR), % 27.6 0 55.2 31.6
p=0.015 p=0.144
Median PFS, months – – 9.4 5.6
HR=2.12p=0.0475
Tabernero J et al, ASCO GI 2008
Stratification factors
• Regions
• ECOG PS
Populations
• Randomized patients n=1217
• Safety population n=1202
• ITT population n=1198
CRYSTAL trial in first-line mCRC
FOLFIRI
Irinotecan (180 mg/m2) + 5-FU (400 mg/m2 bolus+ 2400 mg/m2 as 46-hr continuous infusion) + FA every 2 weeks
Cetuximab + FOLFIRI
Cetuximab IV 400 mg/m2 on day 1, then 250 mg/m2 weekly + irinotecan (180mg/m2) + 5-FU (400 mg/m2 bolus+ 2400 mg/m2 as 46-hr continuous infusion) + FA every 2 weeks
EGFR-expressing metastatic CRC
Van Cutsem E et al, ASCO 2007
R
CRYSTAL trial – Primary endpoint PFSITT population independent review
A retrospective analysis investigated the impact on progression-free survival and response rate of the KRAS mutation status of tumors in the first-line treatment of metastatic CRC treated with FOLFIRI ± cetuximab
Relating KRAS status to efficacy
• Efficacy analyses repeated on KRAS evaluable population
• Genomic DNA isolated from archived tumor material
• Paraffin-embedded, formalin-fixed tissue
• KRAS mutation status of codons 12/13 determined using quantitative PCR-based assay