KRAS/NRAS Mutations Predict Panitumumab Nonresponsiveness in Metastatic CRC

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KRAS/NRAS Mutations Predict Panitumumab Nonresponsiveness in Metastatic CRC
KRAS/NRAS Mutations Predict Panitumumab Nonresponsiveness in Metastatic CRC

SAN FRANCISCO—Adding panitumumab to second-line FOLFIRI chemotherapy is unlikely to improve outcomes for patients with metastatic colorectal cancer (mCRC) tumors harboring RAS mutations in regions of the tumor genome other than at KRAS exon 2, reported authors of a phase 3 clinical trial at the 2014 Gastrointestinal Cancers Symposium.

“These results confirm that it is RAS status that matters, not just KRAS, when determining if panitumumab therapy could be beneficial,” said lead study author Marc Peeters, MD, PhD, professor of oncology at Antwerp University Hospital in Edegem, Belgium. “For patients with a RAS mutation, these findings will spare them the costs and side effects of a treatment that will not improve their outcomes.”

The team used bidirectional Sanger sequencing to detect mutations in KRAS exons (gene-coding regions) 3 and 4, and NRAS exons 2, 3, and 4 with established wild-type mCRC KRAS exon 2.

Related: Gastrointestinal Cancers Resource Center

Patients with wild-type RAS saw superior overall and progression-free survival (OS and PFS) following panitumumab plus chemotherapy, compared to patients with RAS mutations (median OS: 16.2 vs. 11.8 months; median PFS: 6.5 vs. 4.8 months), Dr. Peeters reported.

“For patients in the mutated RAS group, the addition of panitumumab to FOLFIRI resulted in no significant survival differences over FOLOFIRI alone (median OS: 11.8 vs. 11.1 months; median PFS: 4.8 vs. 4.0 months).”

The results are consistent with previous reports for panitumumab treatment and RAS status in mCRC, but represent the first phase 3 trial data for a second-line setting, he noted.

The findings support wider use of “more comprehensive RAS testing” for personalized epidermal growth factor receptor (EGFR) blockade therapies, Dr. Peeters suggested. Testing for RAS mutations allows clinicians to identify patients with mCRC who are most likely to benefit from panitumumab, he explained.

Panitumumab is a fully human monoclonal antibody that targets epidermal growth factor receptor (EGFR) protein. EGFR promotes colorectal tumor growth.

Previous research had shown that EGFR blockade with panitumumab fails to control CRC tumors harboring KRAS mutations at exon 2, a common mutation found in up to 50% of patients.

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).


  1. Peeters M, Oliner K, Price T, et al. Abstract LBA387. Presented at: 2014 Gastrointestinal Cancers Symposium. Jan. 16-18, 2014; San Francisco. 

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