KRAS-G12C Mutation in One Real-Life and Three Population-Based Nordic Cohorts of Metastatic Colorectal Cancer
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., . . . Osterlund, P. (2022). KRAS-G12C Mutation in One Real-Life and Three Population-Based Nordic Cohorts of Metastatic Colorectal Cancer. Frontiers in Oncology, 12, Article 826073. https://doi.org/10.3389/fonc.2022.826073
Published inFrontiers in Oncology
© 2022 Osterlund, Ristimäki, Kytölä, Kuopio, Heervä, Muhonen, Halonen, Kallio, Soveri, Sundström, Keinänen, Ålgars, Ristamäki, Sorbye, Pfeiffer, Nunes, Salminen, Lamminmäki, Mäkinen, Sjöblom, Isoniemi, Glimelius and Osterlund.
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. ...
PublisherFrontiers Media SA
ISSN Search the Publication Forum2234-943X
Publication in research information system
MetadataShow full item record
Additional information about fundingFinska Läkaresällskapet (2016, 2018, 2019, 2020, 2021, 2022), The Finnish Cancer Foundation (2019-2020, 2021, 2022-2023), The Competitive State Research Financing of the Expert Responsibility Area of Tampere, Turku, Helsinki, Oulu and Kuopio University Hospitals (2016, 2017, 2018, 2019, 2020, 2021, 2022), Tampere and Helsinki University Hospital Research Funds (Tukisäätiö 2019, 2020; OOO 2020), The Sigrid Jusélius Foundation (2017, 2021), and The Swedish Cancer Society (2016, 2019) have provided grants. The infrastructure of the RAXO-study, with blood sampling, database, and study nurses, was supported by pharmaceutical companies: Amgen (unrestricted grants, 2012-2020), Lilly (2012-2017), Merck KGaA (2012-2020), Roche Oy (2012-2020), Sanofi (2012-2017), and Servier (unrestricted grant, 2016-2020). Amgen also partly supported the NGS analysis performed in patients included in the Uppsala region cohort. ...
Showing items with similar title or keywords.
Resectability, conversion, metastasectomy and outcome according to RAS and BRAF status for metastatic colorectal cancer in the prospective RAXO study Uutela, Aki; Osterlund, Emerik; Halonen, Päivi; Kallio, Raija; Ålgars, Annika; Salminen, Tapio; Lamminmäki, Annamarja; Soveri, Leena-Maija; Ristamäki, Raija; Lehtomäki, Kaisa; Stedt, Hanna; Heervä, Eetu; Muhonen, Timo; Kononen, Juha; Nordin, Arno; Ovissi, Ali; Kytölä, Soili; Keinänen, Mauri; Sundström, Jari; Nieminen, Lasse; Mäkinen, Markus J.; Kuopio, Teijo; Ristimäki, Ari; Isoniemi, Helena; Osterlund, Pia (Nature Publishing Group, 2022)Background Outcomes after metastasectomy for metastatic colorectal cancer (mCRC) vary with RAS and BRAF mutational status, but their effects on resectability and conversion rates have not been extensively studied. Me ...
Incidence and management of patients with colorectal cancer and synchronous and metachronous colorectal metastases : a population-based study Väyrynen, V.; Wirta, E; Seppälä, T.; Sihvo, E.; Mecklin, J-P.; Vasala, K.; Kellokumpu, I. (John Wiley & Sons, 2020)Background This population-based study aimed to examine the incidence, patterns and results of multimodal management of metastatic colorectal cancer. Methods A retrospective population-based study was conducted on patients ...
Contribution of allelic imbalance to colorectal cancer Palin, Kimmo; Pitkänen, Esa; Turunen, Mikko; Sahu, Biswajyoti; Pihlajamaa, Päivi; Kivioja, Teemu; Kaasinen, Eevi; Välimäki, Niko; Hänninen, Ulrika A.; Cajuso, Tatiana; Aavikko, Mervi; Tuupanen, Sari; Kilpivaara, Outi; van den Berg, Linda; Kondelin, Johanna; Tanskanen, Tomas; Katainen, Riku; Grau, Marta; Rauanheimo, Heli; Plaketti, Roosa-Maria; Taira, Aurora; Sulo, Päivi; Hartonen, Tuomo; Dave, Kashyap; Schmierer, Bernhard; Botla, Sandeep; Sokolova, Maria; Vähärautio, Anna; Gladysz, Kornelia; Ongen, Halit; Dermitzakis, Emmanouil; Bramsen, Jesper Bertram; Ørntoft, Torben Falck; Andersen, Claus Lindbjerg; Ristimäki, Ari; Lepistö, Anna; Renkonen-Sinisalo, Laura; Mecklin, Jukka-Pekka; Taipale, Jussi; Aaltonen, Lauri A. (Nature Publishing Group, 2018)Point mutations in cancer have been extensively studied but chromosomal gains and losses have been more challenging to interpret due to their unspecific nature. Here we examine high-resolution allelic imbalance (AI) ...
Distinct Mutational Profile of Lynch Syndrome Colorectal Cancers Diagnosed under Regular Colonoscopy Surveillance Ahadova, Aysel; Pfuderer, Pauline Luise; Ahtiainen, Maarit; Ballhausen, Alexej; Bohaumilitzky, Lena; Kösegi, Svenja; Müller, Nico; Tang, Yee Lin; Kosmalla, Kosima; Witt, Johannes; Endris, Volker; Stenzinger, Albrecht; von Knebel Doeberitz, Magnus; Bläker, Hendrik; Renkonen-Sinisalo, Laura; Lepistö, Anna; Böhm, Jan; Mecklin, Jukka-Pekka; Seppälä, Toni T.; Kloor, Matthias (MDPI AG, 2021)Regular colonoscopy even with short intervals does not prevent all colorectal cancers (CRC) in Lynch syndrome (LS). In the present study, we asked whether cancers detected under regular colonoscopy surveillance (incident ...
Molecular Basis of Mismatch Repair Protein Deficiency in Tumors from Lynch Suspected Cases with Negative Germline Test Results Olkinuora, Alisa; Gylling, Annette; Almusa, Henrikki; Eldfors, Samuli; Lepistö, Anna; Mecklin, Jukka-Pekka; Nieminen, Taina Tuulikki; Peltomäki, Päivi (MDPI AG, 2020)Some 10–50% of Lynch-suspected cases with abnormal immunohistochemical (IHC) staining remain without any identifiable germline mutation of DNA mismatch repair (MMR) genes. MMR proteins form heterodimeric complexes, giving ...