Refereed journal article or data article (A1)

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




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

PublisherFrontiers Media SA

Publication year2022

JournalFrontiers in Oncology

Journal name in sourceFRONTIERS IN ONCOLOGY

Journal acronymFRONT ONCOL

Article number 826073

Volume number12

Number of pages11

ISSN2234-943X

eISSN2234-943X

DOIhttp://dx.doi.org/10.3389/fonc.2022.826073

URLhttps://doi.org/10.3389/fonc.2022.826073

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/175039451


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 KRASNRAS, 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.

ill hopefully emerge.


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Last updated on 2023-12-05 at 11:04