PMID- 36868178 OWN - NLM STAT- MEDLINE DCOM- 20230331 LR - 20230412 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 178 DP - 2023 Apr TI - KRAS G12C mutated advanced non-small cell lung cancer (NSCLC): Characteristics, treatment patterns and overall survival from a Danish nationwide observational register study. PG - 172-182 LID - S0169-5002(23)00082-X [pii] LID - 10.1016/j.lungcan.2023.02.021 [doi] AB - OBJECTIVES: We aimed to characterize the advanced NSCLC population in terms of KRAS G12C prevalence, patient characteristics, and survival outcomes after the introduction of immunotherapies. MATERIALS AND METHODS: We identified adult patients diagnosed with advanced NSCLC between January 1, 2018 and June 30, 2021 using the Danish health registries. Patients were grouped by mutational status (any KRAS mutation, KRAS G12C, and KRAS/EGFR/ALK wildtype [Triple WT]). We analyzed KRAS G12C prevalence, patient and tumor characteristics, treatment history, time-to-next-treatment (TTNT), and overall survival (OS). RESULTS: We identified 7,440 patients of whom 40% (n = 2,969) were KRAS tested prior to the first line of therapy (LOT1). Among the KRAS tested, 11% (n = 328) harbored KRAS G12C. More KRAS G12C patients were women (67%), smokers (86%), had a high (>/=50%) level of PD-L1 expression (54%), and more frequently received anti-PD-L1 treatment than any other group. From the date of the mutational test result, OS (7.1-7.3 months) was similar between the groups. OS from LOT1 (14.0 months) and LOT2 (10.8 months), and TTNT from LOT1 (6.9 months) and LOT2 (6.3 months) was numerically longer for the KRAS G12C mutated group compared to any other group. However, from LOT1 and LOT2, the OS and TTNT were comparable when stratifying the groups by PD-L1 expression level. Regardless of the mutational group, OS was markedly longer for patients with high PD-L1 expression. CONCLUSION: In patients diagnosed with advanced NSCLC after the implementation of anti-PD-1/L1 therapies, the survival in KRAS G12C mutated patients is comparable to patients with any KRAS mutation, Triple WT, and all NSCLC patients. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Frost, Matilde Grupe AU - Frost MG AD - University of Copenhagen, Faculty of Health and Medicinal Sciences, Copenhagen, Denmark; Department of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark. Electronic address: matilde.tejlbo.frost.01@regionh.dk. FAU - Jensen, Kristoffer Jarlov AU - Jensen KJ AD - Copenhagen Phase IV Unit (Phase4CPH), Department of Clinical Pharmacology and Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark. FAU - Gotfredsen, Ditte Resendal AU - Gotfredsen DR AD - Department of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark. FAU - Sorensen, Anne Mette Skov AU - Sorensen AMS AD - Department of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark. FAU - Ankarfeldt, Mikkel Zollner AU - Ankarfeldt MZ AD - Copenhagen Phase IV Unit (Phase4CPH), Department of Clinical Pharmacology and Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark. FAU - Louie, Karly S AU - Louie KS AD - Amgen Limited, United Kingdom. FAU - Sroczynski, Nicholas AU - Sroczynski N AD - Amgen AB, Denmark. FAU - Jakobsen, Erik AU - Jakobsen E AD - Department of Heart, Lung and Vascular Surgery, Odense University Hospital, Denmark. FAU - Andersen, Jon Lykkegaard AU - Andersen JL AD - Department of Oncology Herlev Gentofte Hospital, Denmark. FAU - Jimenez-Solem, Espen AU - Jimenez-Solem E AD - University of Copenhagen, Faculty of Health and Medicinal Sciences, Copenhagen, Denmark; Department of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark; Copenhagen Phase IV Unit (Phase4CPH), Department of Clinical Pharmacology and Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark. FAU - Petersen, Tonny Studsgaard AU - Petersen TS AD - University of Copenhagen, Faculty of Health and Medicinal Sciences, Copenhagen, Denmark; Department of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230228 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)) RN - 0 (B7-H1 Antigen) RN - 0 (KRAS protein, human) SB - IM MH - Adult MH - Humans MH - Female MH - Male MH - *Carcinoma, Non-Small-Cell Lung/epidemiology/genetics/therapy MH - *Lung Neoplasms/genetics/therapy/metabolism MH - Proto-Oncogene Proteins p21(ras)/genetics/metabolism MH - Mutation MH - Denmark/epidemiology MH - B7-H1 Antigen/metabolism OTO - NOTNLM OT - KRAS mutation OT - Kirsten Rat Sarcoma viral Oncogene homolog DNA with G12C mutation at the protein level (KRAS G12C mutation) OT - Non-Small Cell Lung Cancer (NSCLC) OT - Overall survival OT - Programmed Death Ligand 1 (PD-L1) expression OT - Real world evidence COIS- Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The work was funded by Amgen Inc. The funding was administered by Copenhagen Phase IV Unit, which partly paid the salary of Ditte Gotfredsen, Matilde Grupe Frost, Kristoffer Jarlov Jensen, and Mikkel Zollner Ankarfeldt. Jon Alexander Lykkegaard reports personal fees from Amgen Inc. during the conduct of the study. Anne Mette Skov Sorensen, Erik Jakobsen, Tonny Studsgaard Petersen and Espen Solem Jimenez have nothing to disclose. Nicholas Sroczynski and Karly Louie were employed at Amgen Limited during the conduct of the study. EDAT- 2023/03/04 06:00 MHDA- 2023/03/31 06:42 CRDT- 2023/03/03 18:22 PHST- 2022/11/08 00:00 [received] PHST- 2023/01/16 00:00 [revised] PHST- 2023/02/25 00:00 [accepted] PHST- 2023/03/31 06:42 [medline] PHST- 2023/03/04 06:00 [pubmed] PHST- 2023/03/03 18:22 [entrez] AID - S0169-5002(23)00082-X [pii] AID - 10.1016/j.lungcan.2023.02.021 [doi] PST - ppublish SO - Lung Cancer. 2023 Apr;178:172-182. doi: 10.1016/j.lungcan.2023.02.021. Epub 2023 Feb 28.