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Clinical Outcomes Associated with Single STK11 Mutations and Those Co-occurring with KEAP1 and KRAS Mutations in
Firas Dabbous1, Mehmet Berktas2, Rajrupa Ghosh1
1PPD™ Evidera™ Real-World Data & Scientific Solutions, Thermo Fisher Scientific, Waltham, MA, USA.
Introduction:
Tumors with STK11 mutations and those co-occurring with KEAP1 and KRAS mutations commonly occur in patients with metastatic non-small cell lung cancer (mNSCLC). However, real-world evidence on the associated clinical outcomes is limited. This study assessed real-world progression-free survival (rwPFS) and overall survival (rwOS) among patients with mNSCLC and STK11 (co)-mutations.
Methods:
Adults (≥ 18 years old) diagnosed with de novo stage IV mNSCLC in the USA were identified from the Flatiron Clinico-Genomic Database. The frequencies of STK11 mutation and KEAP1 and KRAS co-mutations were reported. Time-to-event outcomes from mNSCLC diagnosis, including rwPFS and rwOS, were analyzed using Kaplan-Meier estimates and 95% confidence intervals (CIs). Multivariable Cox proportional hazards models assessed associations between STK11 (co)-mutations and rwOS.
Results:
Among 4392 patients with de novo mNSCLC, the frequencies of STK11 mutation and co-mutations in KEAP1, KRAS, and both KEAP1 and KRAS were 16.1%, 6.4%, 8.5%, and 3.7%, respectively. Compared with patients without these mutations, median rwOS was shorter in patients with STK11 mutation (8.6 vs. 12.8 months) and with co-mutations in KEAP1 (6.6 vs. 12.5 months), KRAS (10.1 vs. 12.5 months), and both KEAP1 and KRAS (5.2 vs. 12.5 months). The adjusted risk of mortality was higher in patients with STK11 co-mutations in KEAP1 (hazard ratio [HR] 1.68; 95% CI 1.29, 2.18), KRAS (HR 1.44; 95% CI 1.17, 1.76), and both KEAP1 and KRAS (HR 2.33; 95% CI 1.87, 2.90), compared with those without these mutations. Similar increased mortality risks associated with STK11 co-mutations occurred in patients with PD-L1 tumor proportion score ≥ 1% and non-squamous histology.
Conclusion:
STK11 mutations with KEAP1 or KRAS co-mutations are associated with significantly worse survival outcomes in mNSCLC compared with patients without these co-mutations. These findings underscore the urgent need for targeted therapies to improve prognosis in this high-risk population.
