Frontiers in Oncology (Feb 2022)

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

  • Emerik Osterlund,
  • Ari Ristimäki,
  • Ari Ristimäki,
  • Soili Kytölä,
  • Soili Kytölä,
  • Teijo Kuopio,
  • Teijo Kuopio,
  • Eetu Heervä,
  • Eetu Heervä,
  • Timo Muhonen,
  • Timo Muhonen,
  • Päivi Halonen,
  • Päivi Halonen,
  • Raija Kallio,
  • Raija Kallio,
  • Leena-Maija Soveri,
  • Leena-Maija Soveri,
  • Jari Sundström,
  • Jari Sundström,
  • Mauri Keinänen,
  • Annika Ålgars,
  • Annika Ålgars,
  • Raija Ristamäki,
  • Raija Ristamäki,
  • Halfdan Sorbye,
  • Halfdan Sorbye,
  • Per Pfeiffer,
  • Per Pfeiffer,
  • Luís Nunes,
  • Tapio Salminen,
  • Tapio Salminen,
  • Annamarja Lamminmäki,
  • Annamarja Lamminmäki,
  • Markus J. Mäkinen,
  • Markus J. Mäkinen,
  • Tobias Sjöblom,
  • Helena Isoniemi,
  • Helena Isoniemi,
  • Bengt Glimelius,
  • Pia Osterlund,
  • Pia Osterlund,
  • Pia Osterlund,
  • Pia Osterlund,
  • Pia Osterlund,
  • Pia Osterlund

DOI
https://doi.org/10.3389/fonc.2022.826073
Journal volume & issue
Vol. 12

Abstract

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BackgroundKRAS 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.MethodsPatients 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.ResultsThe 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.ConclusionsIn 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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