Abstract 3193: FGFR4 mutationas a novel biomarker for immunotherapy in patients with non-small cell lung cancer

Abstract

Abstract Background: Cancer immunotherapy, especially immune checkpoint inhibitors (ICIs), has provided a remarkable antitumor effect in non-small cell lung cancer (NSCLC), but only a limited number of patients can derive durable benefit. Therefore, more accurate biomarkers are highly needed. The fibroblast growth factor receptor (FGFR) family of receptor tyrosine kinases is comprised of 4 members (FGFR1-4) that mediate the function of the FGFR ligand family. Although the genomic alterations (GAs) of FGFRs were frequently detected by targeted next-generation sequencing (NGS) and considered as potent oncogenes, their correlation with recognized immune biomarkers and predictive value for ICIs response in NSCLC remains unclear. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor and matched blood samples of 3433 NSCLC patients from OrigiMed were collected for targeted NGS panel sequencing from December 2017 to January 2019. GAs including single nucleotide variations, short and long insertions/deletions, copy number variations, and gene rearrangements were assessed. Genomic data and ICIs treatment outcome of 2 cohorts of NSCLC patients were derived from The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center (MSKCC) databases. Results: GAs of FGFR gene family were detected in 5% (172/3433) of patients with NSCLC in the OrigiMed database, including 84 FGFR1 GAs, 34 FGFR4 GAs, 28 FGFR2 GAs, and 26 FGFR3 GAs. No significant difference was observed in the frequency of FGFR4 GAs within the histologic subtypes. Compared with wild-type (WT), FGFR4 GAs were associated with a significantly higher tumor mutational burden (TMB) (6.55 vs. 4.6 muts/Mb, respectively, p<0.001). Survival analysis from 2 independent cohorts confirmed that patients with FGFR4 GAs had remarkable clinical benefit to ICIs compared with WT patients in both progression free survival (PFS) (13.17 months vs 3.17 months, respectively, p=0.025) and durable clinical benefit (DCB) (80% vs 29.3%, respectively, p=0.03). Furthermore, FGFR4 GAs were an independent risk factor of PFS (HR: 0.22, 95%CI: 0.055-0.92, p=0.037) and overall survival (OS) (HR: 0.23, 95%CI: 0.057-0.92, p=0.038). Conclusion: Our results supported that the FGFR4-mutated NSCLC patients were associated with an increased TMB and favorable response to ICIs. This suggests that GAs of FGFR4 may have implications as a biomarker for guiding ICI treatment. Citation Format: Xiangfeng Jin, Xinglong Fan, Kaihua Tian, Hanlin Xu, Nan Ge, Yafei Wang, Shiyue Zhang, Hui Chen, Shaohua Yuan, Kai Wang. FGFR4 mutationas a novel biomarker for immunotherapy in patients with non-small cell lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3193.