Author of

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  MA25 - Precision Medicine in Advanced NSCLC (ID 352)

  • Event: WCLC 2019
  • Type: Mini Oral Session
  • Track: Advanced NSCLC
  • Presentations: 1
  • Now Available
  • Moderators:Sebastian Defranchi, Karen Kelly
  • Coordinates: 9/10/2019, 14:30 - 16:00, Dublin (1997)

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    MA25.09 - Navigating Anlotinib Precision Therapy Through the Genetic Profiling of Circulating DNA in Non-Small Cell Lung Cancer Patients (Now Available) (ID 1055)

    14:30 - 16:00  |  Author(s): Kai Li
    • Abstract
    • Presentation
    • Slides

    Background
    

    Anlotinib is an oral multi-targeted anti-angiogenic drug, and its clinical predictor for non-small cell lung cancer (NSCLC) patients is still elusive. The aim of this study is to screen predictor for anlotinib via non-invasive genetic profiling of plasma cell free DNA and circulating tumor DNA (cfDNA & ctDNA).

    Method
    

    Tumor-specific target capture to profile the circulating DNA of ALTER0303 (Evaluating NSCLC clinical anti-tumor efficacy through anlotinib therapy) study participants. Acquired mutations were screened out via comparing genetic profiling between baseline (BL) and progression disease (PD), and were used for anlotinib stratification. Based on the sequencing data at BL, tumor mutation index (TMI) was established from three independent predictors germline and somatic mutation burden (G+S MB), nonsynonymous and synonymous mutation burden (N+S MB) and unfavorable mutation score (UMS), and was used for predicting anlotinib responders. In addition, TMI combined with IDH1^Exon4 mutation status also be examined for serving as predictor for anlotinib stratification.

    Result
    

    Our data firstly indicated no benefit (NB, PFS ≤ 45 days) patients can be mainly excluded via analysis of ARID1A and BRCA2 genetic profiling. Secondly, for the no durable benefit (NDB, 45 days < PFS ≤ 130 days) and durable clinical benefit (DCB, PFS > 130 days) patients, harboring lower mutation burden (G+S MB, N+S MB, and UMS) received more benefit from anlotinib therapy. Subsequently, we found the predictor-TMI can predict anlotinib responders upon discovery cohort (Median PFS: 210 days vs 126 days; p = 0.0238; AUC = 0.77), and validation cohort (Median PFS: 210 days vs 127 days; p = 0.0352) and all patients (Median PFS: 210 days vs 127 days; p = 0.0044) more effectively. Furthermore, the IDH1^Exon4 mutation was identified as an unfavorable factor to anlotinib therapy under TMI-based stratification. Lastly, the TMI plus IDH1^Exon4 mutation status predict response to anlotinib significantly (Median PFS: 210 days vs 127 days, p < 0.0001, AUC = 0.90; Median OS: 423 days vs 162 days, p < 0.0001, AUC = 0.80).

    Conclusion
    

    This study provides circulating DNA sequencing-based stratification for underlying anlotinib responders via non-invasive approach, and thus potentially improve clinical outcome for NSCLC patients at 3^rd line.

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