Author of

• 30601

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  P2.01 - Advanced NSCLC (ID 159)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall

  • 30710

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    P2.01-97 - Angiotensin-Converting Enzyme Inhibitor Is Associated with Decreased Survival in NSCLC Patients Treated with PD-1 Checkpoint Blockers (ID 2389)

    10:15 - 18:15  |  Author(s): Soleine Medjbar
    • Abstract

    Background
    

    Angiotensin-converting enzyme (ACE) inhibitors are frequently used to treat hypertension and congestive heart failure. Preclinical evidence shows that ACE plays a role on both innate and adaptive immune responses by promoting macrophages and neutrophils function and the stimulation of antigen presentation, thus suggesting the possibility of anti-tumor immunity through an ACE inhibitor-mediated mechanism. Interactions between ACE inhibitors and immune checkpoint blockers (ICB) have not been currently investigated in cancer patients (pts). Our study evaluated the effect of ACE inhibitors on non-small cell lung cancer (NSCLC) pts treated with PD-1/PD-L1 inhibitors.

    Method
    

    We conducted a retrospective multicohort retrospective analysis of pts treated with PD-1/PD-L1 inhibitors for NSCLC at Dijon Cancer Center, and at the University of Montreal Hospital. Clinical data and co-medications were collected. Groups were defined as pts treated with ACE inhibitor or not with at the time of ICB initiation. PFS and OS were compared between both groups. Statistical analyses were performed using the Kaplan-Meier method. Cox regression analyses were performed separately to adjust for standard prognostic factors. RNA sequencing of several tumors were performed and analyzed using CIBERSORT to determine immune cells infiltration.

    Result
    

    Among 283 pts included (177 pts from Dijon, and 106 pts from Montreal), 27 (10%) received ACE inhibitors. Baseline characteristics were equally balanced in both groups. However, the ACE inhibitor group was more frequently treated with statins, beta blockers and metformin. The ACE inhibitor group had shorter median PFS compared to the control group: 2.5 vs. 3.8 months, p= 0.02 (HR=1.7 CI95% 1.1-2.5). The negative impact of ACE inhibitor group was maintained after multivariate analyses adjusting for known risk factors (HR=1.9 CI95% 1.1-3.5 p=0.02 for PFS and HR=2.3 CI95% 1.2-4.4 p=0.01 for OS). RNA sequencing suggested that ACE inhibitor group tumors had lower M1 macrophages, activated mast cells, NK cells and memory activated T cells thus suggesting an immunosuppressed state.

    Conclusion
    

    ACE inhibitor prescription concomitant to the PD-1/PD-L1 inhibitors treatment is associated with impaired outcome in pts with advanced NSCLC pts. This reduction is independent of standard prognostic factors. Biological correlative analyses suggest a tumor immunosuppressed state in ACE inhibitor group. These results should be validated in larger prospective cohorts.