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Treatment outcome according to tumor RAS mutation status in OPUS study patients with metastatic colorectal cancer (mCRC) randomized to FOLFOX4 with/without cetuximab.
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: The addition of cetuximab to FOLFOX4 significantly improved progression-free survival and response in the first-line treatment of patients (pts) with KRAS codon 12/13 (hereinafter exon 2) wild-type (wt) mCRC. Pts with KRASexon 2 tumor mutations showed no such cetuximab benefit, with a trend for worse outcome. Methods: Available KRAS exon 2 wt tumors from OPUS study pts were screened for 26 mutations (new RAS) in 4 additional KRAS codons (exons 3 and 4) and 6 NRAS codons (exons 2, 3 and 4) using BEAMing technology (5% sensitivity cutoff selected for analysis). Outcome was assessed according to RAS mutation status (KRAS exon 2 + new RAS). Results: Mutation status was evaluable in 118/179 (66%) pts with KRAS exon 2 wt tumors. New RAS mutations were detected in 31/118 (26%) pts. In those with RAS wt tumors, response was significantly improved by the addition of cetuximab to FOLFOX4 (Table). The treatment effect for those with new RAS tumor mutations could not be definitively assessed due to low pt numbers. In pts with any tumor RAS mutation (KRAS exon 2 + new RAS), no benefit from the addition of cetuximab to FOLFOX4 was seen, with a clear trend for worse outcome. Conclusions: Pts with mCRC harboring any activating RAS mutation are unlikely to benefit from the addition of cetuximab to FOLFOX4. Restricting cetuximab administration to pts with tumors wt at all such loci might help further tailoring of therapy to maximize pt benefit. Clinical trial information: NCT00125034.
|New RAS mt*
|Response rate, %||57.9||28.6||53.3||43.8||37.0||50.7|
|Median progression-free survival, months||12.0||5.8||7.5||7.4||5.6||7.8|
|Median overall survival, months||19.8||17.8||18.4||17.8||13.5||17.8|
Abbreviations: cet, cetuximab; HR, hazard ratio; mt, mutant; *RAS evaluable population, N=118; †Subset of the OPUS KRAS evaluable population, N=315; ‡Cochran-Mantel-Haenszel; §log-rank.
Abstracts by Carsten Bokemeyer:
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Presentations by Carsten Bokemeyer:
Cetuximab with chemotherapy (CT) as first-line treatment for metastatic colorectal cancer (mCRC): Analysis of the CRYSTAL and OPUS studies according to KRAS and BRAF mutation status.Meeting: 2010 ASCO Annual Meeting Abstract No: 3506Session: Gastrointestinal (Colorectal) Cancer (Oral Abstract Session)