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Oded Icht



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    P1.04 - Immunooncology (Not CME Accredited Session) (ID 936)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.04-17 - Tumour Burden as a Predictive Tool of Response to Immune Checkpoint Inhibitors (ICI) in Patients with Metastatic Non-Small-Cell Lung Cancer (ID 12467)

      16:45 - 18:00  |  Presenting Author(s): Oded Icht

      • Abstract
      • Slides

      Background

      ICI are a novel class of agents that have revolutionized treatment for patients with metastatic non-small-cell lung cancer (NSCLC). Still, most patients do not benefit from PD-1 axis inhibitors, emphasizing the need for additional markers beyond PDL-1 expression for better selection of patients.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This retrospective, single centre study included all consecutive patients with advanced NSCLC who were evaluated with a FDG-PET scan prior to first administration of an ICI (nivolumab or pembrolizumab) between 1/2016 and 6/2017. Tumour burden was calculated using the total body Metabolic Tumour Volume (MTV) and the sum of all measurable lesions (SOML) with accordance to the RECIST criteria. This study received IRB approval.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 58 patients with histologically proven NSCLC were included. Patients had a median age of 65 years (43-84), 59% were male, 62% had adenocarcinoma and 83% were previously treated with chemotherapy. The median PFS for the entire cohort was 5.7 (1-15.8) months, and the ORR for ICI was 44.8%.

      The median MTV was 12.95 (0-236) millimeter³ and was significantly and inversely associated with longer PFS (p=0.036, 95%CI 1-1.015). The median SOML was 88 (13-305) centimetres, and was significantly and inversely associated with a longer PFS and higher ORR (PFS: P=0.004, 95% CI 1.002-1.011, ORR: OR 0.993 p=0.0067(.

      Additionally, patients with a SOML under 56 CM (first quartile) had a longer PFS compared to patients with a higher disease volume (Table1).

      SOML

      (CM)

      Median PFS

      (months)
      P value
      (compared to 1st quartile)
      1st quartile 56 12.1 -
      2nd quartile 88 5.1 0.017
      3rd quartile 115 4.23 0.036
      4th quartile 305 3.15 0.01

      table 1: some of measurable lesions (in centimeters) and PFS in metastatic NSCLC pateints recieving ICI

      8eea62084ca7e541d918e823422bd82e Conclusion

      In our study, a high tumour burden in patients with advanced NSCLC treated with ICI was associated with a shorter PFS and a lower ORR. This association warrants further prospective evaluation in order to optimize treatment.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.04-30 - A Potential Effect of Diabetes Mellitus and Metformin Use on Efficacy of Immune Checkpoint Inhibitors (ICI) (ID 14072)

      16:45 - 18:00  |  Author(s): Oded Icht

      • Abstract
      • Slides

      Background

      Numerous studies have demonstrated metformin use is associated with decreased cancer risk in the general population, as well as improved overall response rate (ORR), progression free survival (PFS) and overall survival (OS) in cancer patients undergoing chemotherapy.Recent in-vitro studies found several new mechanisms which granted metformin the potential to increase cancer patients' response to immune checkpoint inhibitors (ICI).
      In this study we aim to explore the correlation between the daily use of metformin and benefit from ICI in patients with lung cancer and other solid malignancies.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively evaluated all consecutive patients with metastatic solid malignancies treated with ICI therapy in a single institution between February 2015 and June 2017. Patients' clinical data was obtained from electronic medical records. Cox proportional hazards model and chi squared test were used to determine the associations between metformin use and ORR, median PFS (mPFS) and median OS.

      4c3880bb027f159e801041b1021e88e8 Result

      Of 218 patients included in the analysis (202 NSCLC, 16 non lung cancers), 49 (22.5%) suffered from type 2 diabetes mellitus (T2DM). Of them 33 (15.1%) were treated with metformin and 16 (7.3%) received other, non-metformin therapy for T2DM. Comparison between non-diabetic and diabetic cancer patient groups demonstrated that mPFS was found to be significantly higher in the non-diabetic patients – 6.0 vs. 4.0 months (HR=1.47 [1.03-2.09], p=0.036). ORR was comparable (35.5% vs. 30.6%, p=0.52).
      In the T2DM subgroup - mPFS and HR suggested increased efficacy in the metformin group compared to non-metformin, but the numbers were too small to reach significance 8.0 vs. 3.2 months (HR=0.63 [0.32-1.23], p=0.17). ORR was also numerically higher (36.4% vs. 18.8%, p=0.21).
      In both comparisons, no significant differences were found in OS.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This data suggests T2DM might be associated with decreased efficacy of ICI.

      While several studies demonstrated that diabetic cancer patients receiving chemotherapy gained much benefit with metformin use, the trend we observed regarding metformin use with ICI therapy was milder and should be further explored in larger prospective cohorts.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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