Cetuximab Does Not Improve FOLFOX4 Outcomes for CRC with RAS Mutations

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Cetuximab Does Not Improve FOLFOX4 Outcomes for CRC with RAS Mutations
Cetuximab Does Not Improve FOLFOX4 Outcomes for CRC with RAS Mutations

SAN FRANCISCO—Cetuximab should not be added to first-line FOLFOX4 for patients whose metastatic colorectal cancer (mCRC) harbors RAS mutations, suggests research presented at the 2014 Gastrointestinal Cancers Symposium.

“Patients with mCRC harboring any activating mutation of KRAS or NRAS are unlikely to benefit from the addition of cetuximab to FOLFOX4,” reported Sabine Tejpar, MD, PhD, at the University Hospital Gasthuisberg in Leuven, Belgium, and coauthors. “Restricting cetuximab administration to patients with tumors wt [wild type] at all such loci might enable the further tailoring of therapy to maximize patient benefit.”

The authors screened tumors from 179 patients defined as having wt KRAS codon 12/13, for specific mutations in KRAS exons 3 and 4(8), and NRAS exons 2,3 and 4(18), and assessed patients' treatment outcomes by mutation status.

Mutations at the screened loci were detected in 36 of 118 RAS tumor mutation status–evaluable patients, Dr. Tejpar and coauthors reported.

Related: Gastrointestinal Cancers Resource Center

Patients whose mCRC tumors do not harbor RAS mutations had significantly improved tumor response rates when cetuximab was added to first-line FOLFOX4. “In the RAS wt population, there was benefit associated with the addition of cetuximab to FOLFOX4,” (response rate, 61.1% vs. 30.4%; odds ratio [OR], 3.46; 95% CI: 1.37-8.71; P = 0.008), they reported.

Median progression-free survival (PFS, but not overall survival) among patients with RAS wt tumors was significantly improved with the addition of cetuximab (PFS, 12.8 vs. 5.8 months; hazard ratio [HR], 0.43; 95% CI: 0.21-0.88; P = 0.018).

But for patients with RAS mutations at any tested locus, cetuximab appeared to be associated with significantly shorter PFS (5.6 vs. 7.8 months; HR, 1.59; 95% CI: 1.08-2.36; P = 0.018), according to data presented in the study abstract.

In the overall RAS-mutant population, “there was less favorable clinical outcome and no benefit from the addition of cetuximab to FOLFOX4,” the coauthors concluded.

A total of 36 patients were found to have tumors harboring new RAS mutations, but definitive conclusions for these patients were not offered because of their low numbers, the researchers noted.

The 2014 Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association (AGA) Institute, the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), and the Society of Surgical Oncology (SSO).

References

  1. Tejpar S, Lenz H, Köhne C, et al. Abstract LBA444. Presented at: 2014 Gastrointestinal Cancers Symposium. Jan. 16-18, 2014; San Francisco.

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