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Effect of KRAS and NRAS mutations on treatment outcomes in patients with metastatic colorectal cancer (mCRC) treated first-line with cetuximab plus FOLFOX4: New results from the OPUS study.
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: Patients with KRAS exon 2 codon 12/13 wild-type (wt) mCRC benefit significantly from the addition of cetuximab to first-line FOLFOX4 in relation to response and progression-free survival. Patients with KRAS exon 2 codon 12/13 mutations show no benefit with a trend to worse clinical outcomes. Methods: Tumors from OPUS study patients previously defined as KRAS codon 12/13 wt (n=179) were screened for specific mutations in KRAS exons 3 and 4 (8) and NRAS exons 2, 3, and 4 (18) using BEAMing technology. Treatment outcomes were assessed according to mutation status. Results: RAS tumor mutation status was evaluable for 118/179 (66%) patients. Mutations at the screened loci were detected in 36 (31%) patients. In the RAS wt population, there was benefit associated with the addition of cetuximab to FOLFOX4 (Table). In the overall RAS-mutant population, there was less favorable clinical outcome and no benefit from the addition of cetuximab to FOLFOX4. Conclusions: Patients with mCRC harboring any activating mutation of KRAS or NRAS are unlikely to benefit from the addition of cetuximab to FOLFOX4. Definitive conclusions for patients with new tumor mutations cannot be drawn due to low patient numbers. Restricting cetuximab administration to patients with tumors wt at all such loci might enable the further tailoring of therapy to maximize patient benefit.
(all tested loci)
|New RAS mt†
(any tested locus)
|Response rate, %||61.1||30.4||47.1||36.8||36.2||48.7|
|Median PFS, months||12.0||5.8||7.3||7.4||5.6||7.8|
|Median OS, months||20.7||17.8||14.8||17.8||13.4||17.8|
†RAS evaluable population (n=118). ‡ Subset of the KRAS evaluable biomarkers population (n=315). * Cochran-Mantel-Haenszel. ** Log rank. Abbreviations: cet, cetuximab; HR, hazard ratio; mt, mutant; OS, overall survival; PFS, progression-free survival.
Abstracts by Sabine Tejpar:
Clinical and molecular landscape of metastatic colorectal cancer (mCRC) harboring ALK, ROS1, or NTRK 1, 2, 3 (NTRKs) rearrangements.Meeting: 2017 Gastrointestinal Cancers Symposium | Abstract No: 589
Intratumoral heterogeneity in colorectal cancer: Can histology be used as a guidance for molecular testing?Meeting: 2017 Gastrointestinal Cancers Symposium | Abstract No: 611
Association of a specific innate immune response to DNA damage with DNA repair deficient colorectal cancers.Meeting: 2016 ASCO Annual Meeting | Abstract No: 3035
Educational Book Articles by Sabine Tejpar:
Presentations by Sabine Tejpar:
Mutant KRAS and BRAF gene expression profiles in colorectal cancer: Results of the translational study on the PETACC 3-EORTC 40993-SAKK 60-00 trial.Meeting: 2010 ASCO Annual Meeting Abstract No: 3505Session: Gastrointestinal (Colorectal) Cancer (Oral Abstract Session)
Prognostic and predictive molecular biomarkers in stage II colon cancer - current evidence and future perspectiveMeeting: 2010 ASCO Annual MeetingSession: Biomarker-driven Treatment in Stage II Colon Cancer: When to Hold and When to Fold (Education Session)
Microsatellite instability (MSI) in stage II and III colon cancer treated with 5FU-LV or 5FU-LV and irinotecan (PETACC 3-EORTC 40993-SAKK 60/00 trial).Meeting: 2009 ASCO Annual Meeting Abstract No: 4001Session: Gastrointestinal (Colorectal) Cancer (Oral Abstract Session)