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

Österlund, Emerik; Ristimäki, Ari; Nunes, Luís; Kytölä, Soili; Aho, Sonja; Heervä, Eetu; Uutela, Aki; Lehtomäki, Kaisa; Stedt, Hanna; Halonen, Päivi; Kontiainen, Joel; Muhonen, Timo; Kallio, Raija; Sundström, Jari; Ålgars, Annika; Ristamäki, Raija; Nieminen, Lasse; Sorbye, Halfdan; Pfeiffer, Per; Salminen, Tapio; Nordin, Arno; Lamminmäki, Annamarja; Mäkinen, Markus J.; Sjöblom, Tobias; Isoniemi, Helena; Glimelius, Bengt; Osterlund, Pia
KRAS and NRAS mutations in Nordic population-based and real-world metastatic colorectal cancer cohorts

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

Nature Publishing Group
doi:10.1038/s44276-025-00188-5
URI
https://doi.org/10.1038/s44276-025-00188-5
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Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe202601216063
Tiivistelmä

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.

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