Clinical characteristics and outcomes of patients with metastatic colorectal cancer (CRC) harboring NRAS mutations

Background

NRAS mutations are now being identified because of extended RAS testing prior to EGFR (epidermal growth factor receptor) inhibitor therapy. The clinical implications of NRAS mutation beyond lack of response to anti-EGFR therapy and whether these tumors behave similarly to KRAS mutant (MUT) mCRC are not clear.

Methods

We performed a computerized search for all cases of NRAS MUT mCRC identified at our institution under standard genotyping for anti-EGFR treatment selection from 2010 to 2016. Genotyping was performed either by a mass-spectrometry based assay (Sequenom) to detect hotspot mutations in a panel of 8 genes or (starting 2014) through an exon-capture next generation sequencing assay (MSK-IMPACT) of >300 cancer related genes. A comparison group consisted of all mCRC cases genotyped for RAS mutations at our institution from 2008-2012 (n = 918). All cases were reviewed for patient characteristics, treatment history, and survival.

Results

We identified 87 patients with NRAS MUT mCRC (44% exon 2, 56% exon 3). Four cases had concurrent NRAS and KRAS mutations. Median age at diagnosis, gender, primary tumor site, and stage at diagnosis were similar for NRAS MUT and wild-type (WT) cases. First site of metastasis was similar to that of WT cases and included liver, lung, and peritoneum in 79%, 13%, and 10% of cases, respectively. PI3K pathway alterations consisted of less common alterations (3 mutations in C2 and 1 in helical domain of PIK3CA, 2 AKT1 mutations) and were less frequent than in KRAS MUT mCRC (p 

Conclusions

In this large series of NRAS MUT mCRC, we find that NRAS mutation is significantly associated with shorter OS.

Clinical trial identification

Legal entity responsible for the study

None

Funding

N/A

Disclosure

All authors have declared no conflicts of interest.