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Cited by 23Colorectal Cancer Treatments and StudiesColorectal Cancer Surgical TreatmentsLung Cancer Treatments and Mutations

KRAS-G12C Mutation in One Real-Life and Three Population-Based Nordic Cohorts of Metastatic Colorectal Cancer

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Osterlund, Emerik, Ristimäki, Ari, Kytölä, Soili, Kuopio, Teijo, Heervä, Eetu, Muhonen, Timo, Halonen, Päivi, Kallio, Raija +15 more·2022·Frontiers in Oncology
DOI 10.3389/fonc.2022.826073PMC PMC8889930
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Abstract

Background: KRAS mutations, present in over 40% of metastatic colorectal cancer (mCRC), are negative predictive factors for anti-EGFR therapy. Mutations in KRAS-G12C have a cysteine residue for which drugs have been developed. Published data on this specific mutation are conflicting; thus, we studied the frequency and clinical characteristics in a real-world and population-based setting. Methods: Patients from three Nordic population-based cohorts and the real-life RAXO-study were combined. RAS and BRAF tests were performed in routine healthcare, except for one cohort. The dataset consisted of 2,559 patients, of which 1,871 could be accurately classified as KRAS, NRAS, and BRAF-V600E. Demographics, treatments, and outcomes were compared using logistic regression. Overall survival (OS) was estimated with Kaplan–Meier, and differences were compared using Cox regression, adjusted for baseline factors. Results: The KRAS-G12C frequency was 2%–4% of all tested in the seven cohorts (mean 3%) and 4%–8% of KRAS mutated tumors in the cohorts (mean 7%). Metastasectomies and ablations were performed more often (38% vs. 28%, p = 0.040), and bevacizumab was added more often (any line 74% vs. 59%, p = 0.007) for patients with KRAS-G12C- vs. other KRAS-mutated tumors, whereas chemotherapy was given to similar proportions. OS did not differ according to KRAS mutation, neither overall (adjusted hazard ratio (HR) 1.03; 95% CI 0.74–1.42, reference KRAS-G12C) nor within treatment groups defined as “systemic chemotherapy, alone or with biologics”, “metastasectomy and/or ablations”, or “best supportive care”, RAS and BRAF wild-type tumors (n = 548) differed similarly to KRAS-G12C, as to other KRAS- or NRAS-mutated (n = 66) tumors. Conclusions: In these real-life and population-based cohorts, there were no significant differences in patient characteristics and outcomes between patients with KRAS-G12C tumors and those with other KRAS mutations. This contrasts with the results of most previous studies claiming differences in many aspects, often with worse outcomes for those with a KRAS-G12C mutation, although not consistent. When specific drugs are developed, as for this mutation, differences in outcome will hopefully emerge.

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  • Real-world studies of treatment outcomes in KRAS G12C-mutated metastatic colorectal cancer have reported mixed results; some describe a negative association with prognosis, while others report no difference.

    “Real-world studies of treatment outcomes in KRAS G12C-mutated metastatic colorectal cancer have reported mixed results; some describe a negative association with prognosis, while others report no difference. 8-13”

    From Sotorasib with panitumumab in chemotherapy-refractory KRASG12C-mutated colorectal cancer: a phase 1b trial (2024) · cites this paper as [13]

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Authors
Osterlund, E., Ristimäki, A., Kytölä, S., Kuopio, T., Heervä, E., Muhonen, T., Halonen, P., Kallio, R., Soveri, L.-M., Sundström, J., Keinänen, M., Ålgars, A., Ristamäki, R., Sorbye, H., Pfeiffer, P., Nunes, L., Salminen, T., Lamminmäki, A., Mäkinen, M. J., Sjöblom, T., Isoniemi, H., Glimelius, B., & Osterlund, P.
Affiliations
  • University of Helsinki (FI)
  • Central Finland Health Care District (FI)
  • University of Turku (FI)
  • Oulu University Hospital (FI)
  • Helsinki University Hospital (FI)
  • Fimlab (Finland) (FI)
  • University of Southern Denmark (DK)
  • Uppsala University (SE)
  • Tampere University Hospital (FI)
  • University of Eastern Finland (FI)
  • Karolinska University Hospital (SE)
ORCID
Venue
Frontiers in Oncology
Publisher
Frontiers Media SA
Published
2022-02-16
Volume
12
Pages
826073-826073
ISSN
2234-943X (ISSN-L)
DOI
10.3389/fonc.2022.826073
PMC
PMC8889930
OpenAlex
W4212836433
Cited by
23
References
4
Citations by year
2025: 4 · 2024: 6 · 2023: 10 · 2022: 3
FWCI
2.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Oncology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion, cc-by)
  • Jyväskylä University Digital Archive (University of Jyväskylä) (submittedVersion, cc-by)
  • UTUPub (University of Turku) (submittedVersion, cc-by)
  • Uppsala University Publications (Uppsala University) (submittedVersion, other-oa)
  • NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Työväentutkimus Vuosikirja (submittedVersion)
  • Tampere University Institutional Repository (Tampere University) (submittedVersion, cc-by)
Funders
  • Finska Läkaresällskapet
  • Syöpäsäätiö
  • Tays
  • Turun Yliopistollinen Keskussairaala
  • Helsingin ja Uudenmaan Sairaanhoitopiiri
  • Oulun Yliopistollinen Sairaala
  • Kuopion Yliopistollinen Sairaala
  • Sigrid Juséliuksen Säätiö
  • Cancerfonden
Topics
  • Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
  • Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Keywords
metastatic colorectal cancer, overall survival, anti-EGFR therapy, bevacizumab, metastasectomy, real-world outcomes, predictive biomarkers, treatment patterns, best supportive care, systemic chemotherapy, biologic therapy

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