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  • American Association for Cancer Research (AACR)  (2)
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  • American Association for Cancer Research (AACR)  (2)
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  • 1
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 16_Supplement ( 2020-08-15), p. 3193-3193
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. 3193-3193
    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 & lt;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.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
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  • 2
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 13_Supplement ( 2019-07-01), p. 4056-4056
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 4056-4056
    Abstract: Background: Immunotherapy has played an increasingly important role in the treatment of non-small-cell lung cancer (NSCLC) and it was approved for the first-line treatment of advanced lung cancer. PD-L1 expression and TMB are two important immunotherapy biomarkers, however, the relationship between PD-L1 expression, TMB and clinical features is still unclear. Methods: A total of 205 Chinese NSCLC patients (pts) including 120 males and 85 females with a median age of 61.5 years (range 31-84) were enrolled. Tumor stage was evaluated according to the 8th edition of the AJCC/UICC TNM staging system for NSCLC. FFPE tumor and matched blood samples were collected for NGS based 450[[Unsupported Character - Codename & shy;]]gene panel assay. TMB was assessed by standard NGS algorithms. TMB data (median: 5.4 muts/Mb, range 0.8-68.9 muts/Mb) from 206 lesions were provided for analysis. 172, 16 and 18 lesions tissues were analyzed for PD[[Unsupported Character - Codename & shy;]]L1 expression by IHC with 22C3, 28-8 and ZR3 antibodies, respectively. Results: According to TNM staging system, pts were divided into stage I (44 pts), stage II (20 pts), stage III (40 pts) and stage IV (101 pts). The pathological types of pts are adenocarcinoma (69.4%), squamous cell carcinoma (18.4%) and other types (12.1%). 34.5% of lesions were positive for PD-L1 expression (TPS≥1%), including 25.7% PD-L1(TPS≥10%) and 16.5% PD-L1(TPS≥50%) respectively. Significant differences between males and females were observed in PD-L1 expression (TPS≥1%: 40.8% vs. 25.6%, p & lt;0.05; TPS≥10%: 30.8% vs. 18.6%, p & lt;0.05; TPS≥50%: 20.8% vs. 10.5%, p & lt;0.05). In addition, males had higher TMB than females (median: 8.5 vs. 3 muts/MB, p & lt;0.001). A higher percentage of males than females were identified with TMB≥10 muts/Mb (45.0% vs. 12.8%, p & lt;0.001) and TMB≥20 muts/Mb (11.7% vs. 2.3%, p & lt;0.05). The percentage of PD-L1 positive in advanced pts was higher than in stage I pts (TPS≥1%: 39.5% vs 19.6%, p & lt;0.005; TPS≥10%: 30.7% vs 12.4%, p & lt;0.005; TPS≥50%: 16.1% vs 5.2%, p & lt;0.05). Squamous cell carcinoma had higher TMB than adenocarcinoma (median: 8.5 vs. 3.8 muts/MB, p & lt;0.001). Squamous cell carcinoma had a higher percentage of TMB≥10 muts/Mb than adenocarcinoma (44.7% vs. 23.1%, p & lt;0.01). A low correlation was observed between PD-L1 expression and TMB (p & lt;0.001, r=0.2). Pts with PD-L1 TPS≥10% had higher TMB (median: 10 vs 3.8 muts/Mb, p & lt;0.001) and pts with TMB≥10 muts/Mb had higher percentage of PD-L1 positive expression (50.8% vs 27.0%, p & lt;0.001). Conclusion: In this study, we found the most commonly used two biomarkers for immune checkpoint inhibitors, PD-L1 expression and TMB, may be correlated with gender, stage and pathological type of NSCLC patients. There is also a weak correlation between these two biomarkers. Exploring the relationship between immune biomarkers and clinical features may better guide in screening more suitable patients for immune checkpoint blockade. Citation Format: Yang Yu, Xinglong Fan, Yucheng Wei, Zimin Liu, Zuping Lian, Hongxia Han, Ming Yao, Kai Wang. Correlation analysis between PD-L1 expression, TMB and clinical characteristics in Chinese non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4056.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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