MMDA-10 INTRACRANIAL DISEASE CONTROL WITH SOTORASIB IN KRAS G12C NON-SMALL CELL LUNG CANCER AND PREEXISTING BRAIN METASTASES: A REAL-WORLD COHORT WITH GENOMIC PROFILING

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ID: 324436
2026
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Abstract
Abstract Purpose KRAS mutant lung cancers are associated with an increased incidence of brain metastasis, which are highly morbid. This study attempts to characterize the role of sotorasib, a KRAS G12C targeting small molecule inhibitor, in controlling CNS disease progression in patients with KRAS G12C mutant lung cancers. Methods A single-center retrospective cohort study was conducted examining patients with KRAS G12C mutated lung cancers and brain metastasis treated with sotorasib between January 2018 and February 2025. Individual lesion growth or regression was tracked longitudinally using available MRI while on treatment with sotorasib. Each patient’s intracranial response to treatment was assessed using modified RANO-BM criteria. Kaplan-Meier methodology was used to calculate overall survival and intracranial progression free survival. Genomic analysis of tumor biopsies sequenced by the MSK-IMPACT targeted sequencing panel pre- and post-sotorasib treatment was performed for available samples. Results Twenty lung cancer patients receiving sotorasib with radiologic evidence of intracranial disease were included. A total of 128 brain metastases were present among the entire cohort at baseline. The median number of brain metastases was 4 per patient (range=1-16). The median maximal diameter of these lesions was 5.9mm (range=1.1-28.1mm). The median overall survival (OS) following sotorasib initiation was 6.47 months (95%CI=4.80-8.77). The median iPFS was 4.34 months (95%CI=4.20-n/a). An increased number of brain metastases was associated with shorter overall survival (HR = 1.17, p = 0.011). Prior or concurrent SRS along with sotorasib was significantly associated with improved OS (HR = 0.0115, p = 0.0038). Six patients (30%) treated with sotorasib and SRS demonstrated an absence of new distant CNS lesion development at last follow up. Conclusion Sotorasib demonstrated heterogenous intracranial efficacy in patients with preexisting brain metastasis, with the best results seen in patients receiving sotorasib plus upfront SRS.
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openalex_W7201866882 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Zelalem Demere, Nelson Moss
Journal Neuro-Oncology Advances
Year 2026
DOI
10.1093/noajnl/vdag161.038
URL
https://doi.org/10.1093/noajnl/vdag161.038
Keywords Keywords not found

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