Molecular, clinical and prognostic characterization of double KRAS/PIK3CA (dKP) mutated metastatic colorectal cancer (mCRC)

Background

Molecular screening in mCRC has demonstrated an impact in treatment selection and outcome estimation. KRAS mutations (mut) frequently coexist with PIK3CA mut. Molecular, clinical and prognostic association of the dKP group has not been studied in detail.

Methods

657 mCRC patient records that were eligible for targeted mut profile were reviewed. From Jan 2010 – Jun 2014, mass spectrometry (Sequenom oncogene panel) was performed in 497 samples, and from Jul 2014 – Jul 2015, next generation sequencing (MiSeq amplicon oncogene and tumor suppressors panel) in 160.

Results

dKP mut were found in 82 cases (12.5%), RAS/BRAF/PIK3CA wild type (wt) in 38.4%, RAS mut/PIK3CA wt 38.5%, RAS/BRAF wt/PIK3CA mut 3.4% and BRAF mut 7.2%. PIK3CA mut are enriched in KRAS mut as compared to RAS wt (25% vs. 9%, OR = 3.4, p 

Conclusions

The molecular features of dKP samples such as enrichment in particular KRAS/PIK3CA codons, less co-existing TP53 mut, together with their particular clinical characteristics suggest that the biology of these tumors is different from other genomically-defined groups. Nevertheless, co-occurrence of a PIK3CA mut on top of RAS mut does not significantly impact survival in the metastatic setting.

Clinical trial identification

Legal entity responsible for the study

N/A

Funding

VHIO

Disclosure

J. Tabernero: Consultant/Advisory role: Amgen, Bayer, Boehringer Ingelheim, Celgene, Chugai, Lilly, MSD, Merck Serono, Novartis, Roche, Sanofi, Symphogen, Takeda, Taiho. All other authors have declared no conflicts of interest.