KRAS G12C mutated advanced non-small cell lung cancer (NSCLC): Characteristics, treatment patterns and overall survival from a Danish nationwide observational register study

Matilde Grupe Frost*, Kristoffer Jarlov Jensen, Ditte Resendal Gotfredsen, Anne Mette Skov Sørensen, Mikkel Zöllner Ankarfeldt, Karly S. Louie, Nicholas Sroczynski, Erik Jakobsen, Jon Lykkegaard Andersen, Espen Jimenez-Solem, Tonny Studsgaard Petersen

*Corresponding author for this work

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Abstract

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.

Original languageEnglish
JournalLung Cancer
Volume178
Pages (from-to)172-182
ISSN0169-5002
DOIs
Publication statusPublished - Apr 2023

Bibliographical note

Publisher Copyright:
© 2023 Elsevier B.V.

Keywords

  • Kirsten Rat Sarcoma viral Oncogene homolog DNA with G12C mutation at the protein level (KRAS G12C mutation)
  • KRAS mutation
  • Non-Small Cell Lung Cancer (NSCLC)
  • Overall survival
  • Programmed Death Ligand 1 (PD-L1) expression
  • Real world evidence

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