2023 North America Conference on Lung Cancer (NACLC) - Posters and Abstracts-PP01.095 Daniel Simmons NACLC23 Abstract

PP01.095 Daniel Simmons NACLC23 Abstract

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A study was conducted to investigate the prevalence and clinical outcomes associated with STK11, KEAP1, and KRAS mutations or co-mutations in newly diagnosed patients with metastatic non-small cell lung cancer (mNSCLC) in the United States. The study included adult patients with stage IV NSCLC and known histology/PD-L1 status who were enrolled in the Flatiron clinico-genomic database and excluded those enrolled in clinical trials, with positive/missing EGFR/ALK, other malignancies, mixed histology, or without structured data.<br /><br />The study found that out of the 964 patients included, the prevalence of STK11 mutation (STK11m), KEAP1 mutation (KEAP1m), and KRAS mutation (KRASm) were 18%, 15%, and 35%, respectively. The most common co-mutation observed was KRASm and STK11m, present in 10% of patients, while 4% of patients had all three mutations. The mutations were more common in non-squamous mNSCLC, with STK11m and KEAP1m more prevalent in PD-L1 negative patients, and KRASm more prevalent in PD-L1 positive patients.<br /><br />Despite the association of these mutations with PD-(L)1 inhibitor resistance, a significant proportion of patients with STK11m, KEAP1m, and KRASm received immune checkpoint inhibitor (ICI) mono or combination therapy as first-line treatment. However, the median overall survival (OS) for the overall population was 10.1 months, while OS in patients with STK11m, KEAP1m, and co-mutations ranged from 6.1 to 7.1 months, which was substantially lower than in wild-type patients.<br /><br />The study concludes that STK11, KEAP1, and KRAS mutations and co-mutations are relatively common in mNSCLC patients. However, current treatments, especially in patients with these mutations, are associated with poor OS. Therefore, the study suggests that new treatment options such as PDL1-CTLA4 inhibition or enrollment in clinical trials should be considered to address these harder-to-treat subgroups.

Keywords

STK11 mutation

KEAP1 mutation

KRAS mutation

co-mutations

metastatic non-small cell lung cancer

prevalence

clinical outcomes

PD-L1 status

immune checkpoint inhibitor

overall survival