WCLC 2025 - Posters & ePosters-EP.11.20 Real World-Outcomes of Advanced Non-Squamous NSCLC Patients Treated With First-Line Chemo-Immunotherapy According to KRAS Status

EP.11.20 Real World-Outcomes of Advanced Non-Squamous NSCLC Patients Treated With First-Line Chemo-Immunotherapy According to KRAS Status

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This multicenter retrospective-prospective Italian study assessed real-world outcomes of advanced non-squamous non-small cell lung cancer (nsq-NSCLC) patients treated with first-line platinum-pemetrexed-pembrolizumab chemo-immunotherapy, focusing on the impact of KRAS mutation status. KRAS mutations, present in about 25% of lung adenocarcinomas with p.G12C as the most common variant, were analyzed in 765 patients (443 KRAS wild-type, 121 KRAS G12C-mutated, and 201 other KRAS mutations).<br /><br />Baseline characteristics were generally similar across groups. Notably, bone metastases were more frequent in KRAS mutated patients, while liver metastases were less common. Smoking status showed statistically significant differences, with fewer never-smokers among KRAS mutated patients.<br /><br />Progression-free survival (PFS) was shorter in KRAS mutated patients compared to wild-type (median 8.8 vs. 10.8 months; HR 1.29, p=0.018), driven primarily by non-G12C mutations (HR 1.31, p=0.026), whereas KRAS G12C mutation showed a non-significant trend (HR 1.25, p=0.136). No significant differences were observed in overall survival (OS) or objective response rates between KRAS wild-type and mutated groups or between KRAS G12C and other mutations.<br /><br />The study confirms a potential negative predictive role of KRAS mutations on PFS in this treatment context but finds no statistically significant differences in OS or treatment response. Limitations include lack of detailed data on specific non-G12C KRAS variants and the potential influence of co-mutations. Further research is needed to elucidate the effects of co-mutations and post-progression outcomes.<br /><br />In conclusion, KRAS mutation status may modestly reduce PFS in nsq-NSCLC patients receiving chemo-immunotherapy frontline, but does not significantly impact overall survival or treatment response rates in this real-world cohort.

Asset Subtitle

Fabiana Perrone

Meta Tag

Speaker Fabiana Perrone

Topic Metastatic Non-small Cell Lung Cancer – Immunotherapy

Keywords

non-squamous non-small cell lung cancer

KRAS mutation

p.G12C variant

platinum-pemetrexed-pembrolizumab

chemo-immunotherapy

progression-free survival

overall survival

bone metastases

smoking status

real-world study