KRAS and NRAS mutations in Nordic population-based and real-world metastatic colorectal cancer cohorts

Background KRAS and NRAS mutations (mt) are drivers in metastatic colorectal cancer (mCRC). We studied frequencies, characteristics, treatments, and outcomes of different KRAS mt and NRAS mt in population-based and real-world settings. Methods Three Nordic cohorts were combined and molecularly characterised for KRAS , NRAS , and BRAF -V600E hotspot mutations. Results Of 2649 mCRC patients, 2118 were molecularly classified. KRAS mt were seen in 49%, NRAS mt in 4%, RAS& BRAF wt in 33%, and BRAF -V600Emt in 14%. No differences in clinical characteristics were observed between KRAS mt and NRAS mt. Median overall survival (OS) was longest among RAS& BRAF wt, intermediate among KRAS mt and NRAS mt, and shortest among BRAF -V600Emt (28.3 vs 21.4 vs 26.3 vs 9.2 months, respectively). Among the eight most common KRAS mt, the only clinical difference was that KRAS -G12S had more distant lymph node metastases (38% vs 18–27%, p = 0.041). KRAS -G12S had shorter OS than KRAS -G12V, KRAS -G12C, KRAS -G12A, and KRAS -G13D. The differences were smaller in treatment groups but withstood in multivariable models. The three most common NRAS mt did not differ clinically. Conclusion KRAS mt and NRAS mt are seen in 49% and 4% of mCRC, respectively. No clinically relevant differences were observed between different RASmt. KRAS mt is a common subgroup for which the outcome hopefully can be improved with newly developed drugs.