Author of

• 36267

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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

  • 36274

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    P75.07 - Association of FGFR4 Mutation With Immunotherapy Outcomes in Patients With Cancer (ID 1789)

    00:00 - 00:00  |  Presenting Author(s): Lingshuang Liu
    • Abstract
    • Slides

    Introduction
    

    Biomarker has a significant predictive effect on the efficacy of immunotherapy. PD-L1 expression has been approved by the FDA as a biomarker for pembrolizumab first-line NSCLC treatment, and TMB is also included in the NCCN guidelines. At the same time, there is more and more evidence that mutations in some genes or pathways are also related to the efficacy of immunotherapy. For example, EGFR mutations and ALK fusion mutations were negatively correlated with the efficacy of immunotherapy, and DDR pathway mutations were positively correlated with the efficacy of immunotherapy. This study was applied to discover more biomarker genes related to the efficacy of immunotherapy.

    Methods
    

    Using published data Riziv-240 and MSK-IMPACT, which contained 240 lung cancer patients and 1666 pan-cancer patients with immunotherapy information and genetic testing information, respectively. Riziv-240 was assigned as the exploration cohort. Lung cancer patients in MSK-IMPACT and MSK-IMPACT pan-cancer patients were used as two validation cohorts. Fisher's exact test, log-rank test, and cox regression were used in R 3.5.2 and IBM SPSS Statistic 21.

    Results
    

    Through comparing the genetic information of responders and non-responders in Riziv-240, gene mutations including TET, POLE, ARDI1A and FGFR4 were found significantly different in these two groups. Among them, TET, POLE, ARDI1A have been reported to be related to the efficacy of immunotherapy. In the discovery cohort, the immunotherapy efficacy of patients with FGFR4 mutations was significantly better than that of FGFR4 wild-type patients. Median progression-free survival was 13.2 months (95% CI, 0 to 27.3) and 3.2 months (95% CI, 2.3 to 4.1) (hazard ratio for disease progression or death, 0.23; 95% CI, 0.06 to 0.94; P=0.03). In both validation cohorts, FGFR4 showed superior immunotherapy efficacy compared with FGFR4 wild-type patients. In the pan-cancer validation cohort, median overall survival was not reach in the FGFR4 mutations group and 18 months (95% CI, 15.9 to 20.1) in the FGFR4 wild-type group (hazard ratio for death, 0.47; 95% CI, 0.34 to 0.65; P<0.01). In the lung cancer validation cohort, median overall survival was not reach in the FGFR4 mutations group and 11.0 months (95% CI, 8.9 to 13.1) in the FGFR4 wild-type group (hazard ratio for death, 0.50; 95% CI, 0.26 to 0.97; P=0.04).

    Conclusion
    

    FGFR4 mutations are positively correlated with the efficacy of immunotherapy. These findings may provide clue for future clinical practice.

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