139P KRAS-G12C NSCLC linked to female sex and high risk of CNS metastasis: Real-world data from the National Swedish Lung Cancer Registry 2016-2019

Abstract

KRAS mutations represent common genetic driver aberrations in NSCLC. Real world data on demographics and outcome linked to different KRAS mutation subtypes is crucial as targeted drugs against the p.G12C variant become available in clinical practice. We used data from the National Swedish Lung Cancer Registry to evaluate 6183 patients diagnosed with NSCLC during 2016-2019 with reported NGS-based KRAS-status. Following exclusion of other targetable driver aberrations, three cohorts were studied further with regard to age, sex, smoking status, disease stage, performance status, histology, metastatic patterns and overall survival (OS, from diagnosis); KRAS-G12C (n=848), KRAS-other (n = 1161), driver negative (WT, n = 3349). Study sponsored by Amgen. The prevalence of KRAS driver mutations and KRAS-G12C respectively was 32%/14% in NSCLC, 38%/16% in adenocarcinoma, 28%/13% in NSCLC-NOS and 6%/2% in squamous cell carcinoma. Women were more common in the KRAS-G12C cohort (65%) compared to KRAS-other (59%) and WT (48%). Never smokers were rare in KRAS-G12C (2.5%) as opposed to KRAS-other and WT patients (7.2% and 12.3%). A high percentage of KRAS-G12C patients in stage IV (28%) had CNS metastases at diagnosis compared to KRAS-other or WT (19% and 18%). In stage I–IIIA disease we found no differences in OS between the three cohorts. In stage IV, both KRAS-G12C (5.8 months) and KRAS-other (5.2 months) had shorter median OS than the WT group (6.4 months). Women had better outcome in all stage IV mutational subgroups except in KRAS-G12C where OS was comparable between men and women (median 6.6 vs 6.1 months). Stage IV patients with KRAS-G12C, with and without CNS metastases had similar OS (median 6.1 months vs 6.2 months), as opposed to KRAS-other and WT where CNS metastasis was associated with poorer survival. In an unselected Swedish NSCLC population the KRAS-G12C mutation was associated with female sex, smoking, adenocarcinoma histology and linked to presence of CNS metastases. The relationship between OS, female sex and CNS metastases at diagnosis in the KRAS-G12C subgroup need to be further explored with regard to biological mechanisms and confounding clinical factors.