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Outcomes in patients treated with frontline immune checkpoint inhibition (ICI) for advanced NSCLC with KRAS mutations and STK11/KEAP1 comutations across PD-L1 levels.
- Source :
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Lung Cancer (01695002) . Apr2024, Vol. 190, pN.PAG-N.PAG. 1p. - Publication Year :
- 2024
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Abstract
- • A US nationwide clinicogenomic database was used to investigate KRASm and survival across PD-L1 in mNSCLC undergoing frontline ICI-based treatment. • A significant interaction was seen between KRASm and PD-L1 status. • KRASm was associated with worse survival only in PD-L1 0% tumors. • This association was driven by KEAP1 and STK11 comutations, which were enriched in PDL1 0% In patients with advanced NSCLC (aNSCLC), the impact of KRAS mutations (m) and comutations with STK11 and KEAP1 on outcomes across different PD-L1 levels remains incompletely understood. We aimed to investigate the frequency of KRAS mutations and comutations across PD-L1 levels, and the association between these mutations and survival, stratified by PD-L1 expression. We conducted a nationwide cohort study of patients diagnosed with aNSCLC between 2016 and 2021 treated with frontline (chemo)immunotherapy, who underwent molecular genotyping including KRAS, STK11, and KEAP1. Real-world overall survival (OS) and progression-free survival (rwPFS) were estimated using Kaplan-Meier methodology. Cox multivariable regressions were used to evaluate the association between KRASm and survival across different PD-L1 strata, and to assess whether the association between KRASm and survival differed by PD-L1 level. Finally, within subgroups defined by PD-L1 expression, we used interaction terms to assess whether co-mutations with STK11 and KEAP1 moderated the association between KRAS mutation and survival. Of our 2593-patient cohort, 982 (37.9 %) were KRASm and 1611 (62.1 %) KRASwt. KRASm were enriched in the PD-L1 ≥50 % cohort (334/743, 45 %), but within patients with KRASm, co-mutations with STK11 and KEAP1 were enriched in the PD-L1 0 % cohort. KRASm was associated with significantly worse OS in the PD-L1 0 % cohort compared to the PD-L1 ≥50 % cohort (P for interaction = 0.008). On adjusted analyses stratified by PD-L1, KRASm was associated with worse survival only in the PD-L1 0 % group (OS HR 1.46, p = 0.001). KEAP1 and STK11 comutations were most strongly associated with worse OS in the PD-L1 0 % subgroup; patients with triple KRASm/KEAPm/STK11m PD-L1 0 % NSCLC experienced the worst outcomes. KRASm are associated with worse overall survival in PD-L1 negative NSCLC; however, this association is largely driven by comutations with STK11 and KEAP1, which are enriched in PD-L1 negative tumors. [ABSTRACT FROM AUTHOR]
- Subjects :
- *IMMUNE checkpoint inhibitors
*PROGRAMMED death-ligand 1
*RAS oncogenes
Subjects
Details
- Language :
- English
- ISSN :
- 01695002
- Volume :
- 190
- Database :
- Academic Search Index
- Journal :
- Lung Cancer (01695002)
- Publication Type :
- Academic Journal
- Accession number :
- 176431733
- Full Text :
- https://doi.org/10.1016/j.lungcan.2024.107510