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| |  Addition of Cetuximab Improves Treatment of KRAS Wild-Type Colorectal Tumours: Reported at ASCO By Bruce Sylvester CHICAGO -- June 3, 2008 -- Addition of cetuximab to folinic acid, 5-fluorouracil, and irinotecan (FOLFIRI) achieves a significant treatment effect as first-line treatment of KRAS wild-type metastatic colorectal cancer (mCRC) tumours compared with FOLFIRI alone, according to research presented here at the American Society of Clinical Oncology (ASCO) 44th Annual Meeting. However, patients with KRAS mutant-type tumours do not appear to benefit from the addition of cetuximab to their treatment, researchers reported here on June 1 in the plenary session. "Adding cetuximab to FOLFIRI in treating metastatic colorectal cancer leads to a significant increase in progression-free survival, and the benefit is greater for KRAS wild-type tumours than for tumours that do not have this characteristic," said lead investigator Eric Van Cutsem, MD, University Hospital Gasthuisberg, Leuven, Belgium. "We saw no benefit to patients with KRAS mutant tumours from the addition of cetuximab to FOLFIRI." Previously reported data from the randomised, phase 3 Cetuximab Combined With Irinotecan in First-Line Therapy for Metastatic Colorectal Cancer (CRYSTAL) trial showed a significant improvement in progression-free survival (PFS), overall response, and curative surgery rate with the addition of cetuximab to FOLFIRI in the first-line treatment of mCRC. And in other studies, KRAS mutation status correlated to the outcome in mCRC patients who were treated with cetuximab as a single agent or in combination with irinotecan. To evaluate the influence of KRAS mutation status in first-line treatment with FOLFIRI with or without cetuximab, Dr. Van Cutsem and colleagues evaluated patients in the CRYSTAL study. Archived tumour material was available for 587 of 1,198 patients. The investigators isolated genomic DNA directly from slides (3 x 10 mcm) and used standard methods to determine KRAS mutation status. They analysed data from the 540 KRAS-evaluable subjects to determine treatment effect stratified by KRAS mutation status (wild-type or mutant). They used standard analysis tools to evaluate each subgroup for PFS, the primary endpoint of the study, as well as for overall response. "The population with available tissue for KRAS analysis was representative of the overall [intent-to-treat] population," the researchers noted. They found KRAS mutations in 35.6% of 540 subjects with evaluable samples. Among subjects with KRAS wild-type mutations, they found a statistically significant difference in favour of cetuximab treatment for PFS (P = .0167; hazard ratio [HR] estimate 0.68; 95% CI, 0.051-0.934). The best overall response was seen in the cetuximab-treated KRAS wild-type cohort (59.3% for cetuximab plus FOLFIRI vs 43.2% for FOLFIRI, P = .0025). Subgroup analyses by KRAS mutation status for cetuximab plus FOLFIRI versus FOLFIRI alone showed no significant differences between treatment groups for PFS (P = .75; HR estimate 1.07; 95% CI, 0.71-1.61) or best overall response (P = .46). The investigators concluded, "Cetuximab in combination with standard first-line treatment for metastatic colorectal cancer patients is an important new option in patients with KRAS wild-type tumours." Merck KGaA conducted the CRYSTAL study and provided funding for this new analysis.
[Presentation title: KRAS Status and Efficacy in the First-Line Treatment of Patients With Metastatic Colorectal Cancer (MCRC) Treated With FOLFIRI With or Without Cetuximab: The CRYSTAL Experience. Abstract 2]
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