WCLC 2025 - Posters & ePosters-P1.11.27 Optimal Immunotherapy Regimen for STK11 or KEAP1 Mutant Metastatic Non-Small Cell Lung Cancer

Pdf Summary

This review analyzes seven randomized controlled trials evaluating immunotherapy efficacy in metastatic non-small cell lung cancer (NSCLC) patients harboring STK11 or KEAP1 mutations. These mutations are known to impact treatment outcomes, and their interaction with immunotherapy remains an area of active investigation. The study excluded co-mutations of STK11 and KEAP1 due to limited data.<br /><br />Key findings include that immunotherapy regimens, particularly combinations of immunotherapy plus chemotherapy or dual immune checkpoint blockade, significantly improve overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) compared to chemotherapy alone in this patient subset. The KEYNOTE-042 trial showed pembrolizumab improved ORR and OS; KEYNOTE-189 demonstrated pembrolizumab with chemotherapy enhanced PFS, OS, and ORR. However, trials such as POSEIDON and IMPOWER 150 did not consistently show benefit of certain PD-L1 antibody-based chemoimmunotherapy in STK11 or KEAP1 mutations.<br /><br />Notably, combination checkpoint inhibitors (e.g., CheckMate 227 and CheckMate 9LA) showed efficacy in overcoming resistance linked to these mutations. IMPOWER 150 uniquely indicated benefit in KEAP1 mutant patients using four-drug regimens combining chemotherapy, bevacizumab, and atezolizumab.<br /><br />For patients ineligible for combination therapy, single-agent immunotherapy may offer benefits if PD-L1 expression is positive. The review underscores immunotherapy as a preferred approach over chemotherapy alone for STK11 or KEAP1-mutant metastatic NSCLC, though responses vary, and optimal regimens are still being defined.<br /><br />In conclusion, combined chemoimmunotherapy or dual checkpoint blockade shows promise in improving outcomes for this molecularly defined group, warranting further research to refine treatment strategies and identify responders within this challenging NSCLC population.

Asset Subtitle

Natalie Shammas

Meta Tag

Speaker Natalie Shammas

Topic Metastatic Non-small Cell Lung Cancer – Immunotherapy

Keywords

immunotherapy

metastatic non-small cell lung cancer

NSCLC

STK11 mutation

KEAP1 mutation

chemoimmunotherapy

immune checkpoint blockade

pembrolizumab

progression-free survival

overall survival