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Corentin Richard



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    EP1.01 - Advanced NSCLC (ID 150)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.01-25 - An Interactive Interface for Prediction of Anti-PD-1 Efficacy in Lung Cancer Patients (ID 2460)

      08:00 - 18:00  |  Presenting Author(s): Corentin Richard

      • Abstract

      Background

      The past decade has seen a new field of promising treatments for non-small cell lung cancer patients (NSCLC) with immune checkpoint inhibitors (ICI). Medicine community embarks on a biomarker race to identify the one-quarter of responders and potential hyper-progressors. The assessment of PD-L1 tumor expression by IHC is used to select responder patients and is considered as the gold standard biomarker in many studies but it does not predict the absence of anti-PD-1 efficacy. Recent review from Keenan TE et al. summaries all potential studied markers in literature as intratumoral T cell infiltration, tumor neoantigens or else mismatch repair deficiency. Despite this abundance of potential markers, recommendations only rely on high PD-L1 expression and more recently on high tumor mutational burden (TMB). In this study, we propose estimations of response probability based on the different data that may be available for clinicians according their molecular biology and material means.

      Method

      Based on a cohort of 100 patients with advanced NSCLC treated with nivolumab in second line of treatment, we developed an algorithm enabling the calculation of the probability of survival without progression at 6 or 12 months when treated with ICI. Using Cox proportional hazards multiple regression, we adjusted these three stages of information to estimate the probability of response of a patient based on the type of available data: only clinical data and/or exome analysis and/or RNA sequencing. Stability and predictive ability of these models where evaluated internally and externally through bootstrap procedure.

      Result

      Among the 100 patients, 90 had both somatic and constitutional exome sequencings available and 50 had an RNA sequencing. We built a main model based on clinical and pathological data easily available for clinicians. As mandatory criteria, the age, sex, performance status, tumor histology, routine mutational status and PD-L1 immunohistochimical expression were first included in the predictive model. In addition, RECIST response to previous chemotherapy line and antibiotics usage were added into the initial model as they were described significantly associated with respectively good and poor survival to ICI in previous publications. Additional criterion were obtained thanks to extensive DNA tumor analysis such as TMB, mutations in DNA repair pathways, the number of large deletions and intratumoral TCR clones. A third stage of data was added with CD8A and CD274 RNA expressions obtained by RNA sequencing. Thus, several models are available for clinicians to estimate the probability of survival without progression at 6 or 12 months for their patients according to the type of available data. An interactive on-line interface based on R Shiny enables the questioning of all these models for further predictions.

      Conclusion

      Altogether, these data provide validated and more complex biomarkers according to the type of available data to predict probability of survival without progression to anti-PD-1 in patients with advanced NLCSC. Further predictions can be obtained thanks to a shiny R free and interactive interface available on-line.

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    P1.04 - Immuno-oncology (ID 164)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.04-01 - Body Mass Index and Age Do Not Influence Survival in Patients with Lung Cancers Treated with PD1/PDL1 Immune Checkpoint Inhibitors (ID 2333)

      09:45 - 18:00  |  Presenting Author(s): Corentin Richard

      • Abstract

      Background

      Age and body mass index (BMI) are important factors in patients treated with chemotherapy. However, in the era of immune checkpoint inhibitors (ICI), the importance of these baseline characteristics is unclear. For example, pooled analysis of age did not influence the clinical response to ICI, whereas patients with BMI >35 had better outcomes in melanoma and renal cell carcinoma. More data are needed to clarify the role of these two characteristics in non-small cell lung cancer (NSCLC) patients amenable ICI.

      Method

      We conducted a retrospective analysis of patients treated with anti-PD1 ICI for advanced NSCLC at the Dijon Cancer Center (n=177), University of Montreal University Hospital (n=106) and Quebec Heart and Lung Institute (n=98). BMI and age were considered as continuous or categorical variables. Patients’ baseline characteristics were compared using the Chi-squared test. Survival curves were estimated by the Kaplan-Meier method and compared with the Log-rank test in a univariate analysis. Multivariate cox regression model was used to determine hazard ratios and 95% confidence intervals for progression-free survival (PFS) and overall survival (OS) between the groups, adjusting for other clinicopathologic features.

      Result

      Among 381 patients included, the median BMI was 24.5 (range 16.2-43.4) and 32.7% and 13.6% were classified as overweight or obese respectively. The median age was 66 (range 37-89) and 29% were older than 70 years-of-age. Considering BMI and age as continuous or categorical variables, they were not associated with PFS or OS, with the exception of BMI in the Dijon cohort (continuous: HR=0.95, 95%CI[0.91-0.99]; < 25 vs > 25: HR=0.68, 95%CI[0.47-0.99]). Subgroup analysis and multivariate cox regression did not reveal significant interaction of these two factors with outcomes. There was no difference in toxicity between the groups. ECOG performance status was the only significant factor in the three cohorts.

      Conclusion

      Unlike previously described in the era of chemotherapy, obesity and age were not associated with outcomes in NSCLC patients treated with ICI.

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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
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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  |  Presenting Author(s): Corentin Richard

      • 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.