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

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月21日

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  • Emerik Osterlund,
  • Ari Ristimäki,
  • Luís Nunes,
  • Soili Kytölä,
  • Sonja Aho,
  • Eetu Heervä,
  • Aki Uutela,
  • Kaisa Lehtomäki,
  • Hanna Stedt,
  • Päivi Halonen,
  • Joel Kontiainen,
  • Timo Muhonen,
  • Raija Kallio,
  • Jari Sundström,
  • Annika Ålgars,
  • Raija Ristamäki,
  • Lasse Nieminen,
  • Halfdan Sorbye,
  • Per Pfeiffer,
  • Tapio Salminen,
  • Arno Nordin,
  • Annamarja Lamminmäki,
  • Markus J. Mäkinen,
  • Tobias Sjöblom,
  • Helena Isoniemi,
  • Bengt Glimelius,
  • Pia Osterlund

摘要

Background

KRAS and NRAS mutations (mt) are drivers in metastatic colorectal cancer (mCRC). We studied frequencies, characteristics, treatments, and outcomes of different KRASmt and NRASmt 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. KRASmt were seen in 49%, NRASmt in 4%, RAS&BRAFwt in 33%, and BRAF-V600Emt in 14%. No differences in clinical characteristics were observed between KRASmt and NRASmt. Median overall survival (OS) was longest among RAS&BRAFwt, intermediate among KRASmt and NRASmt, and shortest among BRAF-V600Emt (28.3 vs 21.4 vs 26.3 vs 9.2 months, respectively). Among the eight most common KRASmt, 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 NRASmt did not differ clinically.

Conclusion

KRASmt and NRASmt are seen in 49% and 4% of mCRC, respectively. No clinically relevant differences were observed between different RASmt. KRASmt is a common subgroup for which the outcome hopefully can be improved with newly developed drugs.