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Benjamin Lok



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    ES15 - The Management of Cancer Treatment in Thoracic Malignancy (ID 18)

    • Event: WCLC 2019
    • Type: Educational Session
    • Track: Nursing and Allied Professionals
    • Presentations: 1
    • Now Available
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      ES15.03 - Toxicities of Radiation and Immunotherapy: What We Know (Now Available) (ID 3237)

      11:00 - 12:45  |  Presenting Author(s): Benjamin Lok

      • Abstract
      • Presentation
      • Slides

      Abstract

      Radiotherapy is one of the longstanding pillars of cancer treatment. Immunotherapy is being established a new cancer treatment pillar and represents a momentous advance in the armamentarium of the cancer care health professional. As such, how these two modalities interact with each other is important to understand to allow the healthcare team to identify and manage the accompanying side effects. The objectives of this session are to cover a brief overview of basic radiotherapy, basic tumor immunology, followed by a more extensive review on the current status of radiotherapy and immunotherapy in clinical practice with a significant focus on reviewing the toxicities of radiotherapy, immunotherapy and their combination. The goal is to equip all members of the healthcare team to delivery optimal care for patients that receive these treatment modalities.

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    P1.12 - Small Cell Lung Cancer/NET (ID 179)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.12-15 - PET Imaging of [<sup>18</sup>F]PARP Inhibitor as a Pharmacodynamic Biomarker of Talazoparib in Small Cell Lung Cancer PDXs (ID 1794)

      09:45 - 18:00  |  Presenting Author(s): Benjamin Lok

      • Abstract

      Background

      Inhibitors of poly-(ADP)-ribose polymerase (PARP) are promising therapeutics for small cell lung cancer (SCLC). We tested whether PARP inhibitor (PARPi) target engagement as measured by a radiolabeled PARP inhibitor ([18F]PARPi) has the potential to predict drug efficacy in vivo.

      Method

      Tumor growth inhibition during daily talazoparib treatment was evaluated in mice engrafted with SCLC patient-derived xenografts to evaluate talazoparib efficacy at multiple doses. Mice were intravenously injected with [18F]PARPi radiotracer at multiple time points after single doses of oral talazoparib to quantitatively assess the extent to which talazoparib could reduce tumor radiotracer uptake and PET/CT activity.

      abstract fig 1.jpg

      Result

      A dose range of talazoparib with differential therapeutic efficacy was established, with significant delay in time to reach 1000 mm3 for tumors treated with 0.3 mg/kg (p=0.02) but not 0.1 mg/kg talazoparib. On PET/CT with [18F]PARPi tumor was among the tissues with the highest radioactivity per gram (1.37 ± 0.15 %ID/g), significantly higher than surrounding lung (0.24 ± 0.05 %ID/g, p = 0.007), bone (0.27 ± 0.05 %ID/g, p = 0.007), and muscle (0.24 ± 0.15 %ID/g, p < 0.002). A reduction in [18F]PARPi uptake after talazoparib dosing was consistent with talazoparib clearance, with reduction in PET activity attenuating over 24 hours. Talazoparib target engagement, measured by maximum tumor PET uptake, increased in a dose dependent manner (3.9% vs. 2.1% ID/g for 0.1 and 0.3 mg/kg at 3 hours post-talazoparib, p=0.003) and correlated with PARP enzymatic activity among individual tumors as measured by total tumor PAR (p=0.04, R=0.62 at 1 hour post-talazoparib).abstract fig 2.jpg

      Conclusion

      [18F]PARPi PET imaging appears to model PARP inhibitor pharmacokinetics, correlates with PARP inhibitor pharmacodynamics as measured by tumor PAR levels, and differs significantly between therapeutic and subtherapeutic doses of talazoparib. PET imaging using [18F]PARPi has the potential to be a powerful tool in treatment monitoring by assessing PARP inhibitor target engagement in real-time.