Universität zu Köln

Sebastian, Martin ORCID: 0000-0002-0404-7741, Eberhardt, Wilfried E. E., Hoffknecht, Petra, Metzenmacher, Martin, Wehler, Thomas, Kokowski, Konrad, Alt, Juergen, Schuette, Wolfgang, Buettner, Reinhard, Heukamp, Lukas C., Stenzinger, Albrecht, Jaenicke, Martina, Fleitz, Annette, Zacharias, Stefan, Dille, Stephanie, Hipper, Annette, Sandberg, Marlen, Weichert, Wilko, Groschek, Matthias, von der Heyde, Eyck, Rauh, Jacqueline, Dechow, Tobias, Thomas, Michael and Griesinger, Frank (2021). 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). Lung Cancer, 154. S. 51 - 62. CLARE: ELSEVIER IRELAND LTD. ISSN 1872-8332

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Abstract

Objectives: After decades of unsuccessful efforts in inhibiting KRAS, promising clinical data targeting the muta-tion 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 drug-gable 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 nonG12C 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 Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Sebastian, Martin UNSPECIFIED orcid.org/0000-0002-0404-7741 UNSPECIFIED Eberhardt, Wilfried E. E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoffknecht, Petra UNSPECIFIED UNSPECIFIED UNSPECIFIED Metzenmacher, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Wehler, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Kokowski, Konrad UNSPECIFIED UNSPECIFIED UNSPECIFIED Alt, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Schuette, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Heukamp, Lukas C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stenzinger, Albrecht UNSPECIFIED UNSPECIFIED UNSPECIFIED Jaenicke, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED Fleitz, Annette UNSPECIFIED UNSPECIFIED UNSPECIFIED Zacharias, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Dille, Stephanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Hipper, Annette UNSPECIFIED UNSPECIFIED UNSPECIFIED Sandberg, Marlen UNSPECIFIED UNSPECIFIED UNSPECIFIED Weichert, Wilko UNSPECIFIED UNSPECIFIED UNSPECIFIED Groschek, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED von der Heyde, Eyck UNSPECIFIED UNSPECIFIED UNSPECIFIED Rauh, Jacqueline UNSPECIFIED UNSPECIFIED UNSPECIFIED Dechow, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Thomas, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Griesinger, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-603937
DOI:	10.1016/j.lungcan.2021.02.005
Journal or Publication Title:	Lung Cancer
Volume:	154
Page Range:	S. 51 - 62
Date:	2021
Publisher:	ELSEVIER IRELAND LTD
Place of Publication:	CLARE
ISSN:	1872-8332
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RAS MUTATIONS; G12C MUTATION; ADENOCARCINOMA; SUBTYPE; BIOLOGY; IMPACT Multiple languages Oncology; Respiratory System Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/60393