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Weiping Tao

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    JCSE01 - Joint IASLC-CSCO-CAALC Session (ID 63)

    • Event: WCLC 2019
    • Type: Joint IASLC-CSCO-CAALC Session
    • Track:
    • Presentations: 1
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      JCSE01.19 - Tumor Mutation Score Is More Powerful Than Tumor Mutation Burden in Predicting Response to Immunotherapy in Non-Small Cell Lung Cancer (ID 3433)

      07:00 - 11:15  |  Author(s): Weiping Tao

      • Abstract

      Tumor mutation burden (TMB) and PD-L1 expression are the two important biomarkers for immune checkpoint inhibitors (ICIs) in lung cancer. However, growing evidences are showing that not all mutations, such as EGFR mutation, are favorable factors in predicting clinical outcome of ICIs and the power of TMB, which is unselective, might be attenuated. Therefore, we developed tumor mutation score (TMS) as better biomarker for response of ICIs in non-small cell lung cancer (NSCLC).

      TMS was defined as the number of genes with nonsynonymous somatic mutations. Mutations were detected by targeted next-generation sequencing (NGS) in 240 NSCLC patients treated with anti-PD-(L)1 monotherapy or in combination with anti-CTLA4. Durable clinical benefit (DCB) was defined as complete response (CR)/partial response (PR)/stable disease (SD) that lasted 6 months. TMS, TMB and PD-L1 expression were compared among DCB and no durable benefit (NDB) NSCLC patients.

      The total TMS was significantly correlated with TMB (R=0.98, P<0.001) and performed almost equally to TMB in the analysis. 12 genes and 11 genes (5 sharing genes) were significantly associated with longer progression-free survival (PFS) and response (DCB vs NDB), respectively. The number of mutated genes within these 18 genes were defined as TMS18. In the survival analysis of PFS, the HRs of the high group were TMS19 (HR=0.307, P<0.001), TMB (HR=0.455, P<0.001), and PD-L1 expression (HR= 0.403, P=0.02), separately. Moreover, patients with DCB had significantly higher TMS18 (P<0.001), TMB (P=0.006), and PD-L1 expression (P=0.032). High TMS18 group had highest proportion of CR/PR/SD patients, which was 74.1% (CR/PR/SD: 3/17/20), especially in distinguishing CR patients. Taken together, TMS18 was more powerful than TMB and PD-L1 in predicting response of ICIs in NSCLC.

      Simple transformation from unselective TMB to selective TMS greatly enhanced the power of mutations-based biomarkers. TMS in combination with PD-L1 expression might yield better efficiency in predicting response of ICIs in NSCLC with future validation in larger cohorts.