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Christina Appenzeller



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    Lunch & Poster Display session (ID 58)

    • Event: ELCC 2019
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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      157P - Prognostic impact of the use of antibiotics in patients with advanced non-small cell lung cancer (NSCLC) receiving PD-(L)1 targeting monoclonal antibodies (ID 242)

      12:30 - 13:00  |  Author(s): Christina Appenzeller

      • Abstract

      Background

      Anti-PD-(L)1 monoclonal antibodies (mAb) have changed the therapeutic landscape in patients with advanced NSCLC, still 35-40% of these patients derive no benefit from anti-PD-(L)1 mAb. Antibiotics alter gut microbiota diversity and composition, and may affects antitumor immune responses following immune checkpoint inhibitors (ICI) in NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      We retrospectively included 218 patients with advanced NSCLC receiving anti-PD-(L)1 mAb. Overall survival (OS) (primary endpoint), progression free survival (PFS) and radiological response was compared between patients who received antibiotics within 2 months prior to the start of immunotherapy (ATB+) and patients who did not (ATB-). Assuming a rate of antibiotic comedication of 20% of all patients included, the study had a power of 70% to detect a 35% OS improvement in ATB- patients.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      Patients are well balanced with the exception of PD-L1 immunohistochemical expression that was more frequent in ATB+ compared to ATB- (30% vs. 19%, P = 0.05). ATB+ compared to ATB- was associated with a significantly shorter OS (median OS, 10.6 vs 29.9 months, HR 2.7, 95% CI 1.7-4.1, P < 0.001) and shorter PFS (median PFS 1.4 vs 5.8 months, HR 2.2, 95% CI 1.5-3.4, P < 0.001). In the adjusted model for OS, the following 4 parameters retained a statistically significant prognostic value : ATB+ vs. ATB- (HR 2.8, 95% CI 1.7-4.5, P < 0.001), ECOG performance score >1 vs. 0-1 (HR 2.3, 95% CI 1.4-3.7, P = 0.001), squamous-cell vs. Non squamous-cell histology (HR 2.1, 95% CI 1.4-3.2, P < 0.001) and no prior radiotherapy vs. prior radiotherapy (HR 1.7, 95% CI 1.2-2.6, P = 0.006). ATB+ compared to ATB- was significantly associated with an increased risk of progressive disease as best radiological response (73% vs 41%, P = 0.002).

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      Antibiotic treatment is associated with a reduced clinical benefit from therapy with anti-PD-(L)1 mAb. The negative prognostic value of antibiotics was independent from known prognostic factors. However, further investigation is required on the mechanism behind this observation, with emphasis on the role of the gut microbiota composition in the context of anticancer immune response.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      M. Joerger.

      213f68309caaa4ccc14d5f99789640ad Funding

      Has not received any funding.

      682889d0a1d3b50267a69346a750433d Disclosure

      All authors have declared no conflicts of interest.

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