KRAS G12C Mutant Non-Small Cell Lung Cancer Linked to Female Sex and High Risk of CNS Metastasis: Population-based Demographics and Survival Data From the National Swedish Lung Cancer Registry.

BACKGROUND

Real-world data on demographics related to KRAS mutation subtypes are crucial as targeted drugs against the p.G12C variant have been approved.

METHOD

We identified 6183 NSCLC patients with reported NGS-based KRAS status in the Swedish national lung cancer registry between 2016 and 2019. Following exclusion of other targetable drivers, three cohorts were studied: KRAS-G12C (n = 848), KRAS-other (n = 1161), and driver negative KRAS-wild-type (wt) (n = 3349).

RESULTS

The prevalence of KRAS mutations and the p.G12C variant respectively was 38%/16% in adenocarcinoma, 28%/13% in NSCLC-NOS and 6%/2% in squamous cell carcinoma. Women were enriched in the KRAS-G12C (65%) and KRAS-other (59%) cohorts versus KRAS-wt (48%). A high proportion of KRAS-G12C patients in stage IV (28%) presented with CNS metastasis (vs. KRAS-other [19%] and KRAS-wt [18%]). No difference in survival between the mutation cohorts was seen in stage I-IIIA. In stage IV, median overall survival (mOS) from date of diagnosis was shorter for KRAS-G12C and KRAS-other (5.8 months/5.2 months) vs. KRAS wt (6.4 months). Women had better outcome in the stage IV cohorts, except in KRAS-G12C subgroup where mOS was similar between men and women. Notably, CNS metastasis did not impact survival in stage IV KRAS-G12C, but was associated with poorer survival, as expected, in KRAS-other and KRAS-wt.

CONCLUSION

The KRAS p.G12C variant is a prevalent targetable driver in Sweden and significantly associated with female sex and presence of CNS metastasis. We show novel survival effects linked to KRAS p.G12C mutations in these subgroups with implications for clinical practice.

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure The study was funded by Amgen Ltd Johan Isaksson declares research grants from Amgen Sweden AB. Lecture honoraria from Amgen Sweden, AstraZeneca, BMS, MSD and Roche. Participation in advisory boards for Amgen, AstraZeneca and Roche Anders Berglund declares no conflicts of interest outside funding of the study. Karly Louie was an employee of Amgen Ltd while conducting the research and holds stock options in Amgen and Biomarine. Linda Willén declares lecture honoraria and consulting fees from BMS Arash Hamidian is an employee of Amgen Sweden and holds company stock. Anders Edsjö declares lecture honoraria from Amgen, AstraZeneca, Bayer and Diaceutics Fredrik Enlund declares lecture honoraria from AstraZeneca, BMS, Boehringer-Ingelheim, Novartis, PierreFabre and Pfizer. Maria Planck declares research grants from the Swedish Cancer society, the Sjöberg foundation and the Kamprad foundation outside the scope of this study as well as lecture honoraria from Roche. Anders Vikström declares research support from Boehringer-Ingelheim, lecture honoraria from Amgen, AstraZeneca, Boehringer-Ingelheim, BMS, MSD, Novartis, Pfizer, Roche and Takeda. Travel support from Roche. Advisory board participation from AstraZeneca, Boehringer-Ingelheim, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi and Takeda Mikael Johansson declares no conflict of interest outside study funding Andreas Hallqvist declares research grants from AstraZeneca and Novartis. Lecture honoraria from AstraZeneca, BMS and Roche. Gunnar Wagenius declares no conflicts of interest outside funding of the study. Johan Botling declares research grants from BMS, consulting fees and stock options from Strike Pharma and travel support from Amgen Sweden as well as lecture honoraria from Amgen, AstraZeneca, Boehringer-Ingelheim, BMS, GSK, Illumina, Lilly, MSD, Novartis, Pfizer and Roche.