WCLC 2025 - Posters & ePosters-P1.17.49 Real-World Outcomes With IO and Chemo-IO Demonstrate Unmet Need for 1L KRAS G12C-Mutant Advanced NSCLC in the US

Pdf Summary

This observational study evaluated real-world first-line (1L) treatment patterns and clinical outcomes among US patients with advanced non-small cell lung cancer (NSCLC) harboring KRAS G12C mutations. Utilizing data from deidentified electronic health records (EHR) and a clinico-genomic database (CGDB), the study included 1,227 and 447 patients with KRAS G12C-mutant NSCLC, respectively, diagnosed at Stage IIIB-IV or recurrence and initiating 1L therapy between August 2018 and December 2022.<br /><br />KRAS G12C mutations occur in 10–15% of NSCLC cases and currently lack approved targeted therapies for 1L treatment; thus, immunotherapy (IO) alone or combined with platinum-based chemotherapy (PBC, chemo-IO) are standard options. FDA-approved KRAS G12C inhibitors (sotorasib, adagrasib) are only indicated after prior therapy.<br /><br />Key findings showed that PBC plus pembrolizumab (PBCPembrolizumab) and pembrolizumab monotherapy are the preferred 1L regimens, accounting for about 46.5% and 20.4% of treatments, respectively. Notably, fewer than 40% of patients proceeded to second-line (2L) therapy. Median progression-free survival (PFS) with 1L PBCPembrolizumab was approximately 5 months, with overall survival (OS) ranging 13–16 months. For patients with high PD-L1 expression (≥50%) treated with pembrolizumab monotherapy, median PFS was also around 5 months and OS spanned 20–22 months.<br /><br />Prognostically, brain metastases at diagnosis, poor performance status, STK11 co-mutations, and low PD-L1 expression (1%) correlated with shorter OS. Despite modest differences among subgroups, the generally poor outcomes highlight an unmet clinical need for more effective 1L therapies in KRAS G12C-mutant advanced NSCLC.<br /><br />Limitations include sample size variability and heterogeneous comparison groups across databases, which could influence outcome interpretations. This real-world evidence underscores the necessity for novel therapeutic strategies to improve survival in this patient population. The study was sponsored by Eli Lilly and Company and presented at IASLC 2025 World Conference on Lung Cancer.

Asset Subtitle

Kristin Sheffield

Meta Tag

Speaker Kristin Sheffield

Topic Global Health, Health Services, and Health Economics

Keywords

KRAS G12C mutation

non-small cell lung cancer

first-line treatment

immunotherapy

platinum-based chemotherapy

pembrolizumab

progression-free survival

overall survival

brain metastases

real-world evidence