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KRAS G12C-mutated advanced non-small cell lung cancer: a real-world cohort from the German prospective, observational, nation-wide CRISP Registry (AIO-TRK-0315)

Objectives - After decades of unsuccessful efforts in inhibiting KRAS, promising clinical data targeting the mutation subtype G12C emerge. Since little is known about outcome with standard treatment of patients with G12C mutated non-small cell lung cancer (NSCLC), we analyzed a large, representative...

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Main Authors: Sebastian, Martin (Author) , Eberhardt, Wilfried E. E. (Author) , Hoffknecht, Petra (Author) , Metzenmacher, Martin (Author) , Wehler, Thomas (Author) , Kokowski, Konrad (Author) , Alt, Jürgen (Author) , Schütte, Wolfgang (Author) , Büttner, Reinhard (Author) , Heukamp, Lukas (Author) , Stenzinger, Albrecht (Author) , Jänicke, Martina (Author) , Fleitz, Annette (Author) , Zacharias, Stefan (Author) , Dille, Stephanie (Author) , Hipper, Annette (Author) , Sandberg, Marlen (Author) , Weichert, Wilko (Author) , Groschek, Matthias (Author) , Heyde, Eyck von der (Author) , Rauh, Jacqueline (Author) , Dechow, Tobias (Author) , Thomas, Michael (Author) , Griesinger, Frank (Author)
Format: Article (Journal)
Language:English
Published: 2021
In: Lung cancer
Year: 2021, Volume: 154, Pages: 51-61
ISSN:1872-8332
DOI:10.1016/j.lungcan.2021.02.005
Online Access:Resolving-System, kostenfrei: https://doi.org/10.1016/j.lungcan.2021.02.005
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0169500221000647
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Author Notes:Martin Sebastian, Wilfried E.E. Eberhardt,Petra Hoffknecht, Martin Metzenmacher, Thomas Wehler, Konrad Kokowski, Jürgen Alt, Wolfgang Schütte, Reinhard Büttner, Lukas C. Heukamp, Albrecht Stenzinger, Martina Jänicke, Annette Fleitz, Stefan Zacharias, Stephanie Dille, Annette Hipper, Marlen Sandberg, Wilko Weichert, Matthias Groschek, Eyck von der Heyde, Jacqueline Rauh, Tobias Dechow, Michael Thomas, Frank Griesinger, the CRISP Registry Group
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Summary:Objectives - After decades of unsuccessful efforts in inhibiting KRAS, promising clinical data targeting the mutation subtype G12C emerge. Since little is known about outcome with standard treatment of patients with G12C mutated non-small cell lung cancer (NSCLC), we analyzed a large, representative, real-world cohort from Germany. - Patients and methods - A total of 1039 patients with advanced KRAS-mutant or -wildtype NSCLC without druggable alterations have been recruited in the prospective, observational registry CRISP from 12/2015 to 06/2019 by 98 centers in Germany. Details on treatment, best response, and outcome were analyzed for patients with KRAS wildtype, G12C, and non-G12C mutations. - Results - Within the study population, 160 (15.4 %) patients presented with KRAS G12C, 251 (24.2 %) with non-G12C mutations, 628 (60.4 %) with KRAS wildtype. High PD-L1 expression (Tumor Proportion Score, TPS>50 %) was documented for 28.0 %, 43.5 %, and 28.9 % (wildtype, G12C, non-G12C) of the tested patients; 68.8 %, 89.3 %, and 87.7 % of the patients received first-line treatment combined with an immune checkpoint-inhibitor in 2019. TPS>50 % vs. TPS<1 % was associated with a significantly decreased risk of mortality in a multivariate Cox model (HR 0.39, 95 % CI 0.26−0.60, p=<0.001). There were no differences in clinical outcome between KRAS wildtype, G12C or non-G12C mutations and KRAS mutational status was not prognostic in the model. - Conclusion - Here we describe the so far largest prospectively recruited cohort of patients with advanced NSCLC and KRAS mutations, with special focus on the G12C mutation. These data constitute an extremely valuable historical control for upcoming clinical studies that employ KRAS inhibitors.
Item Description:Gesehen am 28.05.2021
Physical Description:Online Resource
ISSN:1872-8332
DOI:10.1016/j.lungcan.2021.02.005

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