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• W3207098279 abstract "Identification of mutations via next generation sequencing (NGS) associated with worse outcomes could potentially improve prognostication and more clearly identify risk/benefit ratios for specific treatments in a given patient. STK11 and KEAP1 mutations have been recently shown to be associated with worse outcomes in patients with advanced disease receiving immunotherapy, however data regarding patients with unresectable stage III NSCLC who received consolidation durvalumab is limited. We sought to establish the prevalence of such mutations in stage III NSCLC and compare outcomes in a real-world cohort. We retrospectively identified patients with unresectable stage III NSCLC who received consolidation durvalumab following chemoradiation between January 2017 and March 2021 at our institution using a clinical research query tool. We then cross-matched this list with one generated from a comprehensive genomic testing data warehouse solution to identify those who also underwent NGS. Basic demographics, disease-related variables (including PD-L1 expression, TMB, and presence of other known oncogenic driver alleles), and treatment history were captured. Individuals with a STK11 or KEAP1 mutation were placed into one group, while those who were wild type for both genes were placed into the other group. Progression-free survival (PFS) and overall survival (OS) from the time of durvalumab initiation were analyzed using the Kaplan-Meier method and log-rank test. We identified 128 individuals who had a diagnosis of stage III NSCLC and received durvalumab, however of these only 29 had also undergone NGS and were eligible for inclusion. Of these 29, the median age was 66 (IQR: 59, 74), 11 (37.9%) were female, 23 (79.3%) were Caucasian, 4 (13.8%) were African American, and 7 (24.1%) had squamous histology. Median PD-L1 expression was 9% (IQR: 0, 35), and median TMB was 8 mut/Mb (IQR: 4, 10). Other than pack-years (median 46 vs 6, p=0.03), no statistically significant differences in baseline characteristics were seen between the mutation and non-mutation groups (p>0.10). Median follow-up time was 20.6 (95% CI: 11.8, 35.9) months. Of the 29 patients, 7 (24.1%) were found to have mutations in STK11 while 5 (17.2%) were found to have mutations in KEAP1; two patients had co-mutations and thus 10 (34.5%) patients overall had at least one mutation. Median PFS was 6.6 (95% CI: 0.9, 9.7) months in patients with a STK11 or KEAP1 mutation and 9.6 (95% CI: 2.8, 22.7) months without such mutations (p=0.40). Median follow-up was 20.4 (95% CI: 8.9, 34.4) months in patients with mutations and 26.1 (95% CI: 15.4, 37.6) months in patients without mutations (p=0.89). Median OS was NR (95% CI: 0.9, NR) in patients with mutations and 24.5 (95% CI: 15, NR) in patients without mutations. No statistically significant differences in PFS or OS were seen in patients with either a STK11 or KEAP1 mutation receiving consolidation durvalumab for unresectable stage III NSCLC, however our analysis may be underpowered due to a low number of patients receiving NGS testing. Further analysis with a larger sample could potentially have prognostic and therapeutic implications, particularly if certain mutations are shown to have reduced benefit with immunotherapy." @default.
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• W3207098279 date "2021-10-01" @default.
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• W3207098279 title "P27.04 Clinical Outcomes for Patients With Stage III NSCLC and STK11 or KEAP1 Genetic Alterations" @default.
• W3207098279 doi "https://doi.org/10.1016/j.jtho.2021.08.387" @default.
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