KEAP1 mutations in squamous cell lung cancer

• Published in: Journal of clinical oncology Vol. 39; no. 15_suppl; p. e21098
• Main Authors: Koleczko, Sophia, Hillmer, Axel, Bayarassou, Abdel Hakim, Grohé, Christian, Buchenroth, Martin, Kaminsky, Britta, Schulte, Clemens, Michels, Sebastian Yves Friedrich, Schaufler, Diana, Kron, Anna, Riedel, Richard, Westphal, Theresa, Weber, Jan-Phillip, Fischer, Rieke Nila, Merkelbach-Bruse, Sabine, Nogova, Lucia, Buettner, Reinhard, Wolf, Juergen, Scheffler, Matthias
• Format: Journal Article
• Language: English
• Published: 20.05.2021
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2021.39.15_suppl.e21098

Abstract only e21098 Background: KEAP1 mutations have been shown to decrease the efficacy of both chemotherapy (CTX) and immune-checkpoint inhibition (ICI) in lung adenocarcinoma. However, few is known about their impact on systemic treatment of squamous cell lung cancer (SqCC). The aim of this study was to assess the impact of KEAP1 mutations on systemic treatment outcome in SqCC. Methods: Tumor biopsies of SqCC patients were analyzed within the German Network Genomic Medicine (NGM) using a next-generation DNA sequencing (NGS) panel comprising 17 genes. In subsets, PD-L1 expression was tested with immunohistochemistry (IHC). MET amplification and FGFR1 amplification was tested with fluorescence in situ hybridization (FISH). Overall survival was estimated using Kaplan Meier statistics. For comparisons, we used log rank. A cohort with KEAP1 wild-type patients from the same panel served as control group. Results: Out of 1399 SqCC patients analyzed, 151 had a KEAP1 mutation (11%). The most common co-occurring mutations besides TP53 were PTEN, KRAS and NFE2L2. The median overall survival (OS) of stage IV KEAP1 mutated patients (n = 82) compared to stage IV control group patients (n = 82) was 7.3 vs. 11.4 months (hazard ratio (HR) 0.87 [95% confidence interval (CI) 0.62-1.23], p = 0.43). The addition of a second treatment line with ICI led to marked OS improvements in both KEAP1 mutant patient group (18.7 vs. 6.6 months, HR 0.11, [95% CI 0.04-0.25], p < 0.0001) and control group (20.3 vs. 5.0 months, HR 0.12 [95% CI 0.06-0.24], p < 0.0001). PD-L1 expression did not differ significantly in both groups. Conclusions: KEAP1 mutations occur commonly in SqCC patients and do not impact the efficacy of ICI in terms of OS. To identify prognostic markers for response to ICI further research is needed.