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Xiangyun Wang



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    P75 - Immunotherapy (Phase II/III Trials) - Misc. Topics (ID 248)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Immunotherapy (Phase II/III Trials)
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P75.11 - Potential Predictive Value of TERT Mutation Status for Response to Immunotherapy in Cancer Patients (ID 2158)

      00:00 - 00:00  |  Presenting Author(s): Xiangyun Wang

      • Abstract
      • Slides

      Introduction

      Immunotherapy has been one of the standard treatment options for lung cancer. Biomarkers such as PD-L1 and TMB have a certain predictive role on the efficacy. At the same time, studies also found that EGFR mutations and ALK fusions were inversely related to the efficacy of immunotherapy. The MYSTIC trial evaluated the mutations of STK11, KEAP1, ARID1A, and KRAS and their correlation with immune efficacy. The results showed that STK11 and/or KEAP1 mutations had poor immunotherapy outcomes, while ARID1A mutations were associated with better immunotherapy efficacy. Exploring more efficacy-related genes is of great significance for precision immunotherapy.

      Methods

      Statistical analysis of genomic data from 240 Lung cancer samples and 1666 pan-cancer samples obtained from public cohort data (Riziv-240 and MSK). Both cohorts contained data of patients treated with anti-PD(L)1 and anti-CTLA4. The Riziv-240 cohort was used as a discovery set and the pan-cancer cohort was used as a validation set. Kaplan-Meier survival analysis and multivariate Cox regression models were applied with SPSS 21.

      Results

      By comparing the mutation maps of responders and non-responders in Riziv-240, TERT were found to be significantly different between the two groups. In both cohorts, samples with TERT mutations exhibited significantly better outcomes than those without TERT mutations. TERT mutations were significantly associated with better prognosis in the discovery cohort (median progression-free survival, 9.1 [95%CI, 4.2-14.0] vs 3.1 [95%CI, 2.4-3.8] months; hazard ratio for death, 0.51; 95% CI, 0.27-0.97, log-rank test, P = .035. In the MSK validation cohort, median overall survival was 22.0 months [95% CI, 15.7-38.3] in the TERT mutations group and 16.0 months [95% CI, 13.7-18.3] in the TERT wild-type group (hazard ratio for death, 0.78; 95% CI, 0.67-0.90 ; log-rank test, P<0.01). The prognostic significance of TERT mutation identified in the Riziv-240 cohort was validated in the MSK cohort.

      Conclusion

      These findings indicate that TERT mutations may be associated with better immunotherapy response. These findings may provide clue for guiding immunotherapy treatment for cancer patients.

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