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Robin Cornelissen



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    ES08 - Critical Concerns in Screening (ID 11)

    • Event: WCLC 2019
    • Type: Educational Session
    • Track: Screening and Early Detection
    • Presentations: 1
    • Now Available
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      ES08.01 - Participation of the Target Population in Lung Cancer Screening (Now Available) (ID 3191)

      13:30 - 15:00  |  Presenting Author(s): Robin Cornelissen

      • Abstract
      • Presentation
      • Slides

      Abstract

      Participation of the Target Population in Lung Cancer Screening

      Robin Cornelissen, MD, PhD.

      Erasmus MC cancer institute

      Rotterdam, The Netherlands

      The two largest randomized controlled trials performed, The National Lung Screening Trial (NLST) and the Nederlands-Leuvens Longkanker ScreeningsONderzoek (NELSON) 1,2, proved that lung cancer screening using low dose CT scan, resulted in a significant reduction in lung cancer mortality. Following the results of the NLST trial, lung cancer screening was initiated in the United States and Canada. However, the uptake of lung cancer screening is poor, with only 3% to 4% of all eligible persons participating in the implemented screening program 3. Given more recent positive results of the NELSON study that were presented at the World Conference on Lung Cancer last year in Toronto, lung cancer screening is now considered in many countries across the globe. This low uptake of lung cancer screening is however a cause of concern.

      The reasons for the low participation rate are multi-factorial. The novelty of the lung cancer screening program is such a factor, resulting in lower uptake and might be the easiest one to address. The identification of the target population is more challenging due to the fact that the population to be screened is more defined than just age and sex. In addition, the lower socioeconomic status, which presents a significant portion of the to be screened population, and those who face barriers to care present a major challenge for implementing a successful screening program with a satisfactory uptake rate.

      Several strategies have been proposed to improve lung cancer screening uptake.

      In the socioeconomically deprived and heavy smoking communities, lung cancer is perceived as an uncontrollable disease 4, while cure rates in yearly screening programs lead to a cure in the majority of patients when lung cancer is detected 5,6. Therefore, public awareness of the curability of lung cancer when screening programs are implemented could boost the participation rate.

      Mobile lung cancer testing in supermarket car parks proved to be a successful pilot 7. This strategy avoids difficulties relating to the distance of travel, lack of public transport available, and the cost of either the journey itself or hospital parking. This strategy is currently explored in a larger cohort.

      One potential intervention that is being evaluated in clinical trials to improve the uptake and implementation of lung cancer screening is a patient navigator. A navigator can be a layperson, a medical assistant, or a nurse who will directly contact potential candidates for lung cancer screening for enrollment 3.

      The Accelerate, Coordinate, Evaluate (ACE) Programme, initiated in the United Kingdom, is an early diagnosis of cancer initiative focused on testing innovations that either identify individuals at high risk of cancer earlier 8. This program consists of several individual programs in different regions of the UK, of which The Liverpool Healthy Lung Programme is a participant. Among other goals, this initiative tries to improve uptake in the hard to reach cohort. They used general practitioners’ records to invite participants meeting the criteria to a ‘Lung Health Check’. This ‘Lung Health Check’ is a novel approach that may overcome or minimize the emotional barriers associate with the term “lung cancer screening”. This method resulted in an uptake level up to 40% 9. This initiative is an example that a higher uptake rate is indeed possible, even in the hard to reach population.

      At the IASLC World Conference on Lung Cancer in Barcelona, the issues regarding participation of the target population in lung cancer screening will be addressed and possible strategies will be discussed to overcome these challenges. As lung cancer screening is yet to be implemented in the majority of countries worldwide, we now have a unique opportunity to test and apply these strategies to successfully implement lung cancer screening in order to reduce lung cancer mortality.

      References

      1. The National Lung Screening Trial Research Team. Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening. N Engl J Med. 2011;365(5):395-409. doi:10.1056/NEJMoa1102873

      2. Koning HD, Aalst CVD, Haaf KT, Oudkerk M. PL02.05 Effects of Volume CT Lung Cancer Screening: Mortality Results of the NELSON Randomised-Controlled Population Based Trial. J Thorac Oncol. 2018;13(10):S185. doi:10.1016/j.jtho.2018.08.012

      3. Triplette M, Thayer JH, Pipavath SN, Crothers K. Poor Uptake of Lung Cancer Screening: Opportunities for Improvement. J Am Coll Radiol JACR. 2019;16(4 Pt A):446-450. doi:10.1016/j.jacr.2018.12.018

      4. Quaife SL, Marlow LAV, McEwen A, Janes SM, Wardle J. Attitudes towards lung cancer screening in socioeconomically deprived and heavy smoking communities: informing screening communication. Health Expect Int J Public Particip Health Care Health Policy. 2017;20(4):563-573. doi:10.1111/hex.12481

      5. Survival of Patients with Stage I Lung Cancer Detected on CT Screening. N Engl J Med. 2006;355(17):1763-1771. doi:10.1056/NEJMoa060476

      6. Jonnalagadda S, Bergamo C, Lin JJ, et al. Beliefs and attitudes about lung cancer screening among smokers. Lung Cancer Amst Neth. 2012;77(3):526-531. doi:10.1016/j.lungcan.2012.05.095

      7. Wise J. Mobile lung cancer testing in supermarket car parks is to be expanded. BMJ. 2017;359:j5450. doi:10.1136/bmj.j5450

      8. Proactive Approaches to Individuals at High Risk of Lung Cancer; Accelerate, Coordinate, Evaluate (ACE) Programme. V1.1a.; 2018. https://www.cancerresearchuk.org/sites/default/files/ace_proactive_lung_report_with_economic_evaluation_final_version_1.1a.pdf. Accessed July 9, 2019.

      9. Ghimire B, Maroni R, Vulkan D, et al. Evaluation of a health service adopting proactive approach to reduce high risk of lung cancer: The Liverpool Healthy Lung Programme. Lung Cancer. 2019;134:66-71. doi:10.1016/j.lungcan.2019.05.026

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    MA05 - Update on Clinical Trials and Treatments (ID 123)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Mesothelioma
    • Presentations: 1
    • Now Available
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      MA05.09 - Real-World Data of Nivolumab and Pembrolizumab in Chemotherapy Pre-Treated Mesothelioma Patients (Now Available) (ID 1918)

      13:30 - 15:00  |  Author(s): Robin Cornelissen

      • Abstract
      • Presentation
      • Slides

      Background

      Both nivolumab and pembrolizumab have shown positive results in phase II studies in patients following chemotherapy in mesothelioma patients. However, these studies were done in a limited number of patients with strict inclusion criteria, while reports show a difference between real life and study setting.

      Method

      In our mesothelioma center, we treated patients that progressed during or after chemotherapy treatment with nivolumab 3mg/kg once every 2 weeks independent of PD-L1 expression or with pembrolizumab 200mg once every 3 weeks when PD-L1 expression was ³1%, both in Early Patient Access programs. All patients were pre-treated with at least one cycle of platinum/folate treatment. CT scan evaluation was done using modified RECIST every 6 weeks.

      Result

      In total, we treated 78 patients with nivolumab and 13 patients with pembrolizumab. Median age of the patients was 71 years (29-85) at start of the checkpoint inhibitor treatment, 80 (88%) were male. Performance status was ECOG 0 in 19 patients, ECOG 1 in 57 patients, ECOG 2 in 9 patients. Data analysis thus far showed 9 partial responses (10%) and 31 patients with stable disease (29%) and therefore a disease control rate of 39% at twelve weeks of treatment. Median progression free survival is 2.4 months and median overall survival 6,3 months. Median duration of response had not been reached yet. These data will be updated for the meeting. Two cases of pseudoprogression were seen on checkpoint inhibition therapy where progression according to modified RECIST was followed by response during continuation of PD-1 therapy. Toxicity was in line with historical data.

      Conclusion

      We believe that this large dataset, using real-world data, can truly give an insight in the clinical benefit of these immune checkpoint inhibitors. In comparison with the published phase I and II trials on nivolumab and pembrolizumab, the response rates appear to be lower in a real-life setting. However, clinically meaningful and durable responses are seen in a population that has no other proven therapy options.

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    MA12 - New Frontiers from Pathology to Genomics (ID 138)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Mesothelioma
    • Presentations: 1
    • Now Available
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      MA12.09 - Checkpoint Inhibitors Synergize with Dendritic Cell-Therapy in Pre-Clinical Models and Mesothelioma Patients (Now Available) (ID 2425)

      14:00 - 15:30  |  Author(s): Robin Cornelissen

      • Abstract
      • Presentation
      • Slides

      Background

      Malignant Pleural Mesothelioma (MPM) is a lethal, treatment resistant neoplasm. Checkpoint inhibitors (CI) have shown promising clinical effects in a minority of patients. It is hypothesized that low response rates to CI are correlated to low numbers of tumor-infiltrating T-cells in MPM patients. Dendritic cell (DC) therapy instigates an immune response and activates tumor-specific T-cells. DC therapy has proven to be effective in pre-clinical models and in a subset of MPM patients. Upregulation of PD-L1 and PD-1 co-inhibitory checkpoints may suppress DC-therapy induced anti-tumor immune response and limit clinical efficacy. To investigate this, we conducted a preclinical and clinical study to evaluate the clinical and immunological effects of DC therapy combined with CI.

      Method

      Immune competent CBA/J mice were orthotopically injected with a syngeneic mesothelioma cell line. Mice were treated with DC-therapy alone or in combination anti-PD-L1 antibodies at high tumor load when DC-monotherapy was found to be ineffective. Peripheral blood and tumors were obtained for flow cytometric analysis and survival was monitored.
      In a clinical setting, nine patients that received DC therapy were sequentially treated with CI. Progression free survival (PFS) was determined from start of CI, using the modified RECIST criteria.

      Result

      Tumors of mice treated with DC-therapy exhibited a three-fold increase in CD8+ T-cell infiltration which was paralleled by heightened expression of PD-L1 on tumor cells (r2=0.69, p=0.0015). Whereas both anti-PD-L1 and DC-monotherapies were ineffective in prolonging survival in our model, combination immunotherapy did (median OS: 24 vs 35 days, p=0.0063). Immune monitoring analyses demonstrated a synergistic increase in proliferation and activation of circulating T-cell following combination therapy. In the clinical trial 3 patients had partial response, 5 patients had stable disease and 1 patient had progressive disease. Median PFS was 5,2 months and median OS was 17,5 months. Currently 3 patients are still alive and two patients are still progression free. There were no grade 3/4 adverse events. PD-L1 expression in tumor biopsies was increased after DC therapy in two of the three responders to CI.

      Conclusion

      In a murine model the synergy between DC therapy and CI was proven and efficacy was driven by activation of CD4+ and CD8+ positive cells. In humans, CI after DC therapy is safe and feasible. Disease control was seen in 8 out of 9 patients treated with CI after DC therapy. DC therapy induces tumor-specific CD8+ T-cell proliferation which is correlated to PD-L1 expression on tumor cells and possibly synergizes with CI treatment.

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    P1.06 - Mesothelioma (ID 169)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Mesothelioma
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.06-06 - EORTC 1205: Randomized Study of Pleurectomy/Decortication (P/D) Preceded or Followed by Chemotherapy in Malignant Pleural Mesothelioma (ID 2511)

      09:45 - 18:00  |  Author(s): Robin Cornelissen

      • Abstract
      • Slides

      Background

      P/D is considered a valid surgical approach in selected pts with resectable MPM with less morbidity than extrapleural pneumonectomy. The procedure is however, poorly standardized and never radical, and is hence preferably preceded or followed by systemic chemotherapy.

      EORTC 1205 aims at comparing the optimal sequencing of chemotherapy with P/D with regard to overall treatment time and feasibility.

      Method

      Functionally operable treatment-naïve pts with T1-3 N0-2 epithelial or biphasic mesothelioma and PS 0-1 are randomized between adjuvant (arm A) and neo-adjuvant chemotherapy (arm B). Chemotherapy in both arms consists of 3 cycles of cisplatin and pemetrexed at standard dosage and with premedication. P/D is performed by experienced thoracic surgeons in credentialed centers. Strict timelines between both procedures apply and surgical quality is audited with intra-operative mapping and imaging and comprehensive registration of complications. Primary endpoint in the intention-to-treat population is successful completion of the multimodality treatment within 20 weeks of randomisation and being alive with no signs of PD and/or persistent grade III-IV toxicity.

      Result

      As of April 10, 2019, 30 pts of the required sample size of 64 have been randomized and 17 operated. Baseline patient and tumor characteristics appear well balanced sofar (table).

      Characteristics and treatment results as per 1/04/2019

      Table

      Arm A

      Arm B

      All

      N

      16

      14

      30

      Male gender (%)

      56

      71

      63

      Median age (y)

      62

      66

      64

      WHO PS 0/1

      10/6

      7/7

      17/13

      TNM Stage 1/2/3 at presentation

      6/6/4

      9/2/3

      15/8/7

      % administered 3 cycles of chemotherapy

      88

      100

      94

      N operated

      9

      8

      17

      Median time between randomization and 1st treatment modality (weeks)

      2.9

      1.6

      2.0

      Median time between 1st and 2nd treatment modality

      5.7

      11.0

      10.1

      N completed treatment

      9

      8

      17

      Median overall treatment time in those completing treatment

      23.7

      18.7

      21.3

      Conclusion

      Trial accrual proceeds on schedule and last patient will be included in 2020. A protocol amendment will allow carboplatin/pemetrexed as induction regimen. An updated analysis on all included patients as per 1/08/2019 will be presented at the meeting.

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