WCLC 2025 - Posters & ePosters-P1.11.69 Efficacy of Immunotherapy ± Chemotherapy in Metastatic NSCLC with KRAS, STK11, or KEAP1 Mutations: A Network Meta-Analysis

P1.11.69 Efficacy of Immunotherapy ± Chemotherapy in Metastatic NSCLC with KRAS, STK11, or KEAP1 Mutations: A Network Meta-Analysis

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This network meta-analysis evaluated the effectiveness of immune checkpoint inhibitors (ICIs) in metastatic non-small cell lung cancer (NSCLC) patients harboring KRAS, STK11, and KEAP1 mutations. These mutations are common and influence tumor immune environment and response to therapy. The study reviewed 8 randomized controlled trials including 7,220 patients, of whom 61.7% were mutation-evaluable.<br /><br />Key findings include:<br /><br />1. ICIs provide a survival advantage over chemotherapy (CT) in patients with KEAP1, STK11, and KRAS mutations.<br />2. Dual ICI combined with chemotherapy (dual ICI + CT) showed the greatest overall survival (OS) benefit in KEAP1-mutant NSCLC (HR 0.48 vs CT, with 72% ranking probability), suggesting this approach helps overcome the immunosuppressive tumor microenvironment associated with KEAP1 mutations.<br />3. ICI monotherapy (PD-1/PD-L1 inhibitors alone) provided the most benefit in STK11-mutant NSCLC (HR 0.56, 65% ranking probability) and KRAS-mutant NSCLC (HR 0.42, 82% ranking probability). This indicates monotherapy ICIs may be preferable for these subgroups.<br />4. Among KRAS mutations, the G12C variant showed particularly strong responses to ICI monotherapy (HR 0.28).<br />5. The impact of co-mutations (presence of multiple mutations simultaneously) remains unclear and requires further study.<br />6. Current biomarkers such as PD-L1 immunohistochemistry guide therapy, but biomarkers for selecting dual ICI therapy remain lacking.<br />7. Ongoing clinical trials, including the TITAN trial, are expected to clarify optimal treatment strategies for these genetically defined NSCLC subsets.<br /><br />In conclusion, mutation-specific immunotherapy approaches can improve outcomes in metastatic NSCLC. Dual ICI plus chemotherapy is most beneficial in KEAP1-mutant tumors, while ICI monotherapy is favored for KRAS and STK11 mutations. Personalized treatment based on mutation profiling represents a promising direction to overcome resistance and enhance survival in NSCLC.

Asset Subtitle

Skyler Taylor

Meta Tag

Speaker Skyler Taylor

Topic Metastatic Non-small Cell Lung Cancer – Immunotherapy

Keywords

immune checkpoint inhibitors

non-small cell lung cancer

KRAS mutation

STK11 mutation

KEAP1 mutation

dual ICI plus chemotherapy

ICI monotherapy

overall survival

tumor microenvironment

personalized immunotherapy