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

Abstract

<h3>Background</h3><p><em>KRAS</em> and <em>NRAS</em> mutations (mt) are drivers in metastatic colorectal cancer (mCRC). We studied frequencies, characteristics, treatments, and outcomes of different <em>KRAS</em>mt and <em>NRAS</em>mt in population-based and real-world settings.</p><h3>Methods</h3><p>Three Nordic cohorts were combined and molecularly characterised for <em>KRAS</em>, <em>NRAS</em>, and <em>BRAF</em>-V600E hotspot mutations.</p><h3>Results</h3><p>Of 2649 mCRC patients, 2118 were molecularly classified. <em>KRAS</em>mt were seen in 49%, <em>NRAS</em>mt in 4%, RAS&<em>BRAF</em>wt in 33%, and <em>BRAF</em>-V600Emt in 14%. No differences in clinical characteristics were observed between <em>KRAS</em>mt and <em>NRAS</em>mt. Median overall survival (OS) was longest among RAS&<em>BRAF</em>wt, intermediate among <em>KRAS</em>mt and <em>NRAS</em>mt, and shortest among <em>BRAF</em>-V600Emt (28.3 vs 21.4 vs 26.3 vs 9.2 months, respectively). Among the eight most common <em>KRAS</em>mt, the only clinical difference was that <em>KRAS</em>-G12S had more distant lymph node metastases (38% vs 18–27%, <em>p</em> = 0.041). <em>KRAS</em>-G12S had shorter OS than <em>KRAS</em>-G12V, <em>KRAS</em>-G12C, <em>KRAS</em>-G12A, and <em>KRAS</em>-G13D. The differences were smaller in treatment groups but withstood in multivariable models. The three most common <em>NRAS</em>mt did not differ clinically.</p><h3>Conclusion</h3><p><em>KRAS</em>mt and <em>NRAS</em>mt are seen in 49% and 4% of mCRC, respectively. No clinically relevant differences were observed between different RASmt. <em>KRAS</em>mt is a common subgroup for which the outcome hopefully can be improved with newly developed drugs.</p>