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• W2898559706 abstract "Mutations in LKB1/STK11 may predict a poor response to immunotherapy in NSCLC. We previously showed that pretreatment neutrophil-to-lymphocyte ratio (NLR) >5 predicted a poor response to immunotherapy in NSCLC. We evaluated the impact of STK11 mutation (MT) alone, and co-existing MTs in KRAS and TP53 on outcomes in patients (pts) treated with immunotherapy at the University of Pennsylvania. The role of NLR was also evaluated. Patients with metastatic NSCLC that underwent NGS and who received 2nd-line immunotherapy were identified (2/2013 – 12/2016). Patient demographics, tumor characteristics, and outcomes were analyzed from the electronic medical record. Chi-square and the Wilcoxon Rank-Sum test were used to assess correlation between NLR and MT status. Median overall survival (mOS) and median progression free survival (mPFS) times are estimated from Kaplan-Meier curves. A Cox proportional hazard model (HR) was used to assess the effect of mutation status on survival outcomes. 110 pts were included with the following MT status: 5 STK11, 16 KRAS, 29 TP53, 13 KRAS/TP53, 7 KRAS/STK11, 9 TP53/STK11, 7 KRAS/TP53/STK11, 24 no STK11, KRAS or TP53 MT. In univariate and multivariable analyses, STK11 MT was not independently associated with mPFS or mOS after immunotherapy. Among pts with TP53 MT, the presence of a STK11 MT was associated with improved mPFS (4.3 vs. 2 mo, HR 0.416, p=0 .035, (95% CI 0.18 –0.94)) and statistically similar mOS (13.1 vs 6.8 mo, HR 0.43, p=0.09 (95%CI 0.16–1.14)) compared with STK11 wild type (WT). Conversely, among pts with KRAS MT, the presence of a STK11 MT was associated with similar mPFS (2.2 vs 2.8 mo, HR 1.64, p=0.247 (95% CI 0.7–3.8)) and mOS (3.5 vs 7.7 mo, HR 2.3, p=0.09 (0.16–1.14)) compared with STK11 WT. NLR did not correlate with MT status. After stratifying for NLR (<5 and >5), the effect of STK11 MT on mOS in the TP53 MT group was amplified in pts with NLR<5 (n=46, HR 0.05, p=0.021, 95% CI 0.004-0.63) compared to TP53 MT with STK11 WT (HR 4.3, p=0.036 (95% CI 1.1-16.9)). STK11 mutation status alone does not correlate with pre-treatment NLR and is not independently associated with survival outcomes after immunotherapy. PFS following immunotherapy is improved in patients with co-existing TP53 and STK11 MT compared to STK11 WT. An OS benefit after immunotherapy is amplified in patients with NLR<5, TP53 MT, and STK11 co-MT. * Authors Marmarelis and Bange contributed equally" @default.
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• W2898559706 date "2018-10-01" @default.
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• W2898559706 title "P1.01-64 Impact of STK11 Co-Mutation on Outcomes Following Immunotherapy Among Patients with TP53 and KRAS Mutated Stage IV NSCLC" @default.
• W2898559706 doi "https://doi.org/10.1016/j.jtho.2018.08.620" @default.
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