2023 Targeted Therapies of Lung Cancer Meeting (Poster)-P1.17. Clinical and Genomic Predictors of Response and Toxicity to Sotorasib in a Real-World Cohort of Patients with Advanced KRAS G12C-Mutant Non-small Cell Lung Cancer

P1.17. Clinical and Genomic Predictors of Response and Toxicity to Sotorasib in a Real-World Cohort of Patients with Advanced KRAS G12C-Mutant Non-small Cell Lung Cancer

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This document presents the results of a multicenter, retrospective analysis of 105 patients with advanced KRAS G12C-mutant non-small cell lung cancer (NSCLC) who were treated with sotorasib outside of clinical trials. The study aimed to identify clinical and genomic features associated with response, progression-free survival (PFS), overall survival (OS), and toxicity to sotorasib.<br /><br />The median duration of follow-up was 13.1 months, and the analysis included patients from Memorial Sloan Kettering Cancer Center, NYP/Columbia, and NYU. The study analyzed the co-mutation status of TP53, STK11, and KEAP1 using various genomic sequencing techniques.<br /><br />The real-world response rate to sotorasib was 28%, and the median real-world PFS was 5.3 months. OS was estimated to be 12.6 months. The presence of KEAP1 co-mutations was associated with shorter OS, while STK11 co-mutations were not significantly associated with outcomes. Severe sotorasib-related toxicity, particularly hepatotoxicity, was predominantly observed in patients who had recent exposure to anti-PD-(L)1 therapy.<br /><br />The study highlights the need for a deeper understanding of the features associated with response and toxicity to sotorasib to inform future drug development and treatment sequencing in clinical practice. It suggests that the activity of sotorasib in real-world settings aligns with the findings of previous prospective studies.<br /><br />The findings emphasize the importance of considering baseline co-mutation status and recent systemic therapy exposures when managing sotorasib treatment in the clinic. The study provides valuable real-world data on the clinical activity and toxicity of KRAS G12C inhibitors, filling a gap in current knowledge.<br /><br />In conclusion, this study provides insights into the clinical and genomic features of response and toxicity to sotorasib in patients with advanced KRAS G12C-mutant NSCLC outside of clinical trials. The data contribute to our understanding of the use and management of sotorasib in routine practice and may guide future research and treatment strategies.

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Rohit Thummalapalli, Memorial Sloan Kettering Cancer Center, United States

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Speaker Rohit Thummalapalli, Memorial Sloan Kettering Cancer Center, United States

Topic Poster Listing

Keywords

multicenter analysis

retrospective analysis

KRAS G12C-mutant NSCLC

sotorasib

response rate

progression-free survival

overall survival

toxicity

co-mutation status

real-world data