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Shun Lu



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    FP12 - Tumor Biology and Systems Biology - Basic and Translational Science (ID 188)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Tumor Biology and Systems Biology - Basic and Translational Science
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP12.13 - Therapeutic Index Predicts Clinical Outcome of both Treated and Treatment-Naïve NSCLC Patients Receiving Targeted- and Immune-Therapy (ID 1931)

      00:00 - 00:00  |  Author(s): Shun Lu

      • Abstract
      • Slides

      Introduction

      Recent studies have reported that the more molecular matches, the better prognosis of clinical treatments is. “Matching score” based on a targeted panel is such an index to evaluate the prognosis of previously treated cancer patients receiving targeted- and immune-therapy, while no similar scoring system has been established for treatment-naïve patients. This research aims to construct a new therapeutic index (T-Index) to predict clinical prognosis for both treatment-naïve and treated NSCLC patients receiving targeted- and immune-therapy.

      Methods

      Whole exome sequencing (WES, ~39Mb CDS of over 18,000 genes) and targeted sequencing (TS, ~1.1Mb CDS of 457 genes) were conducted on tumor samples from 102 stage IV NSCLC patients (treated N=32, treatment-naïve N=70) before targeted- (N=84) and immune-therapy (N=18) from 2018 to 2019. Molecular feature shared by WES and TS (SNV/Indel, CNV and tumor mutation burden (TMB)), and WES-specific molecular features (HLA genotyping, tumor neoantigen burden (TNB), loss of heterozygosity (LOH) and intra-tumoral heterogeneity (ITH)) were analyzed to identify prognostic predictors, and T-Index of WES and TS was each calculated. The association of both T-Indexes with objective response rate (ORR) and progression-free survival (PFS) were analyzed and compared. The cutoff of 0.5 was chosen according to the minimum P value approach.

      Results

      ORR and PFS were significantly higher and longer in patients with T-Index>0.5 than those with T-Index<=0.5 in previously treated patients (N=39) using WES (p=7e-0.4 for ORR, p=0.005 for PFS), but not using TS (p=0.388 for ORR, p=0.119 for PFS) (Figure 1A and 1C). In the treatment-naïve patients (N=70, targeted N=62, immunotherapy N=8), ORR in patients with T-Index>0.5 was significantly higher than those with T-Index<=0.5 using both WES (73.5% vs. 31.8%, p=0.002, Figure 1B)and TS (73.9% vs. 36.4% p=0.004, Figure 1D). A higher T-Index was also an independent predictor of longer PFS in WES(8.4mo vs. 5.5mo,p=0.012)and TS(9.5mo vs. 7.4mo,p=0.035)for treatment-naïve patients (Figure 1B and 1D).figure-20200825.png

      Conclusion

      Our results showed that T-Index by WES including non-canonical biomarkers, TNB, HLA genotyping, LOH and ITH, is significantly associated with clinical outcome whether in treatment-naïve or previously treated patients. Since TS are more practical for companion diagnostics in clinical, a new version of sequencing panel which covers non-canonical biomarkers related to immunotherapy listed above is needed to be developed and tested with the study going forward.

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