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Joachim G Aerts



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    Lunch & Poster Display session (ID 58)

    • Event: ELCC 2019
    • Type: Poster Display session
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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      154P - Renal toxicity from platinum/pemetrexed and pembrolizumab in the era of combination therapy (ID 558)

      12:30 - 13:00  |  Author(s): Joachim G Aerts

      • Abstract
      • Slides

      Background

      Recently, the phase 3 keynote-189 trial showed that in previously untreated patients with advanced non-squamous NSCLC without targetable mutations, the progression-free and overall survival were significantly longer with addition of pembrolizumab to chemotherapy than with chemotherapy alone. Both chemotherapy and pembrolizumab can give renal toxicity, which can be a major challenge in the clinical setting.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      In a prospective multicenter observational real-life cohort study [Visser Eur Respir J 2018], we evaluated the incidence of acute/chronic kidney disease (AKD/CKD), its related treatment discontinuation frequency and associated clinical variables with AKD in patients with stage IIIB/IV NSCLC treated with platinum/pemetrexed. In addition, the Keynote 189 toxicity data was used for the combination treatment. We thereafter reviewed literature to generate an algorithm for diagnosis and treatment in increased creatinine levels.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      149 patients received pemetrexed platinum, of whom 44 patients (30%) continued maintenance. During induction therapy 48 patients (50%) treated with cisplatinum/pemetrexed developed AKD and 15 patients (29%) treated with carboplatin/pemetrexed. During maintenance 13 patients (30%) developed AKD, leading to CKD and treatment discontinuation in eight patients (62%). In the Keynote 189 trial combining pembrolizumab with chemotherapy, nephritis has been reported in 1,7% of patients in any grade (1,5% grade 3-4). However, when looking at an increased blood creatinine in the group that was treated with carboplatin, a total of 12,2% of patients showed any increase (0,7% grade 3-4).

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      Increased blood creatinine levels from pemetrexed and pembrolizumab is a common entity, probably more common in a real-life setting. This elevation is clinically challenging in a population that receives three agents that can cause a creatinine increase. Currently, there are no markers to distinguish between renal failure due to chemotherapy of immunotherapy. We will present an algorithm based on current knowledge for clinicians as guidance for renal dysfunction in patients treated with chemotherapy and pd-(l)1 checkpoint inhibitors.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      The authors.

      213f68309caaa4ccc14d5f99789640ad Funding

      Has not received any funding.

      682889d0a1d3b50267a69346a750433d Disclosure

      D. Dumoulin: Speakers fee: BMS, Roche, Pfizer, Novartis. R. Cornelissen: Consultancy: Roche, Boehringer Ingelheim, BMS, MSD; Speakers fee: Roche, Pfizer, Boehringer Ingelheim, Novartis, BMS. J.G. Aerts: Advisory boards: BMS, Boehringer Ingelheim, MSD, AstraZeneca, Eli Lilly, Takeda, Amphera; Stock owner: Amphera B.V. All other authors have declared no conflicts of interest.

      cffcb1a185b2d7d5c44e9dc785b6bb25

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      22P - Paclitaxel/ carboplatin/ bevacizumab in non-small cell lung cancer patients induces peripheral effector CD8 T cell proliferation that could be prone for treatment with checkpoint inhibitors (ID 384)

      12:30 - 13:00  |  Author(s): Joachim G Aerts

      • Abstract
      • Slides

      Background

      Checkpoint inhibitors targeting programmed death receptor (PD)-1 or PD-ligand 1 (PD-L1) became the cornerstone in the treatment of advanced NSCLC. Several phase III trials showed a better overall survival by treating with combination chemotherapy and checkpoint inhibition, suggesting that addition of chemotherapy increased the response to checkpoint inhibitors. Recently, peripheral blood biomarkers such as Ki67+PD-1+CD8 cells were found to be predictive for clinical outcome with PD-1 treatment. Knowing more about immune modulatory capacities of chemotherapy can help us to design better treatment strategies. We investigated the immune-modulatory effects of paclitaxel/carboplatin/bevacizumab (PCB), focusing on known immune populations associated with response to checkpoint inhibitors in peripheral blood.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      In the NVALT 12 study, 223 patients with advanced NSCLC were enrolled to receive PCB, with or without nitroglycerin patch. At baseline and after the first and second treatment cycle, peripheral blood was drawn. By flow cytometry, the proportions of T cells and several subsets and co-inhibitory receptors of these, B cells and monocytes were determined.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      6 weeks after starting treatment with PCB, the proportions of T cells were significantly increased compared to baseline values. Within the T cells subsets, proliferation of CD4 T cells remained stable whereas proliferation of CD8 T cells (Ki67+) were significantly increased. The proliferating Ki67+ CD8 T cells expresses more PD-1 compared to non-proliferating CD8 T cells. However, patients with >2 fold increased proliferation of T cells did not show a better outcome.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      Paclitaxel/ carboplatin/ bevacizumab induces proliferation of CD8 T cells which expresses more co-inhibitory checkpoint molecules. Progression free and overall survival was unchanged by this increase on its own, showing the rationale to combine PCB with checkpoint inhibition in lung cancer, as used in Impower 150.

      b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification

      NCT01171170.

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Legal entity responsible for the study

      The authors.

      213f68309caaa4ccc14d5f99789640ad Funding

      NVALT.

      682889d0a1d3b50267a69346a750433d Disclosure

      D. Dumoulin: Speakers fee: BMS, Roche, Pfizer, Novartis. A-M.C. Dingemans: Advisory boards, lectures: Roche, Eli Lilly, Boehringer Ingelheim, AstraZeneca, Pfizer, BMS, Amgen, Novartis, MSD, Takeda (honoraria to institution). J.G. Aerts: Advisory boards: BMS, Boehringer Ingelheim, MSD, AstraZeneca, Eli Lilly, Takeda, Amphera; Stock owner: Amphera B.V. All other authors have declared no conflicts of interest.

      cffcb1a185b2d7d5c44e9dc785b6bb25

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    Mini Oral session I (ID 60)

    • Event: ELCC 2019
    • Type: Mini Oral session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/11/2019, 08:00 - 08:50, Room A
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      196O - STELLAR: Final updated results of a phase II trial of TTFields with chemotherapy for unresectable malignant pleural mesothelioma (ID 567)

      08:00 - 08:50  |  Author(s): Joachim G Aerts

      • Abstract
      • Presentation
      • Slides

      Background

      Tumor Treating Fields (TTFields), an anti-mitotic, regional treatment approved for glioblastoma utilizes low intensity, alternating electric fields delivered non-invasively to the tumor using a portable medical device. In-vitro, human mesothelioma cells were highly susceptible to TTFields.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      The trial accrued 80 patients with unresectable, previously untreated mesothelioma. Patients were treated with continuous 150 kHz TTFields (>18h/day) in combination with pemetrexed and cisplatin or carboplatin. Inclusion criteria included ECOG PS of 0-1 and pathologically proven mesothelioma. The primary endpoint was overall survival (OS). A visual analog scale was used to assess EOCG performance status and cancer-related pain assessed until disease progression. The sample size provided 80% power with two-sided alpha of 0.05 to detect an increase in median OS of 5.5 months compared to historical controls (Vogelzang, JCO 2003).

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      All 80 patients had a minimum follow up of 12 months. Median age was 67 (range 27-78), 84% were male and 44% (35 patients) had an ECOG PS of 1. 66% (53 patients) had epithelioid histology, similar to the Vogelzang study. Median OS was 18.2 months (95% CI 12.1-25.8) versus 12.1 months in the historical control. Median OS for epithelioid patients was 21.2 months (95% CI 13.2-25.8). ECOG score was stable during the first year of follow up. Median time to deterioration in performance status was 13.1 months. Average score of pain was lower compared to baseline during the first 7 months of the treatment and was higher later on the study, with a median time to a clinical significant 33% increase in pain of 8.4 months. No device-related serious adverse events (AEs) were reported. Expected TTFields-related dermatitis was reported in 46% (37 patients). Four patients (5%) had grade 3 dermatitis.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      The study met primary endpoint of significant extension of overall survival in previously untreated mesothelioma patients. TTFields was not associated with a decrease in performance status or an increase in pain for the duration of TTFields use. TTFields in combination with chemotherapy is efficacious in malignant pleural mesothelioma compared to historical data.

      b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification

      NCT02397928.

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Legal entity responsible for the study

      Novocure.

      213f68309caaa4ccc14d5f99789640ad Funding

      Novocure.

      682889d0a1d3b50267a69346a750433d Disclosure

      G.L. Ceresoli, F. Grosso: Travel funds: Novocure. All other authors have declared no conflicts of interest.

      cffcb1a185b2d7d5c44e9dc785b6bb25

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    The future of I-O in advanced NSCLC (ID 16)

    • Event: ELCC 2019
    • Type: Specialty session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/11/2019, 11:00 - 12:30, Room A
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      Cell-based I-O in NSCLC (TIL, TCRs, CARs, NK): Is there a role? (ID 40)

      11:00 - 12:30  |  Presenting Author(s): Joachim G Aerts

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    Treatment related pneumonitis in lung cancer patients (ID 12)

    • Event: ELCC 2019
    • Type: Multidisciplinary Interactive session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/11/2019, 08:00 - 08:50, Room W
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      The respiratory and medical oncology perspective (ID 31)

      08:00 - 08:50  |  Presenting Author(s): Joachim G Aerts

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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