Virtual Library

 x 
My Library Virtual Library FAQ

Start Your Search

D. Fennell



Author of

  • +

    MO09 - Mesothelioma I (ID 120)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track:
    • Presentations: 1
    • +

      MO09.06 - Malignant Pleural Mesothelioma in the UK National Lung Cancer Audit: An analysis of 8503 cases (ID 916)

      16:45 - 16:50  |  Author(s): D. Fennell

      • Abstract
      • Presentation
      • Slides

      Background
      The National Lung Cancer Audit is run jointly by the Royal College of Physicians and The Information Centre for health and social care with the aim of recording outcomes in lung cancer (and mesothelioma) on a population scale, explaining the wide variations seen within the UK and between the UK and other countries and ultimately improving outcomes. This abstract presents results for England only, focusing on mesothelioma.

      Methods
      All patients with mesothelioma seen in in secondary care 2006-2011 were analysed. A hierarchy of diagnosis from surgical histology to non-surgical histology to clinical diagnosis was used to exclude patients with potentially conflicting diagnoses. These records were further analysed to extract data on age/sex distribution, referral source, histological subtype, treatment regime and survival rates.

      Results
      There were 8,503 patients with mean age 72yrs (83% male), representing around 65% of expected incident cases (a substantial number diagnosed at autopsy and not included in the audit). 45% have right-sided disease, 28% were left-sided, and 1% were bilateral (data missing in 26%). The majority of patients (47%) were referred by their primary care physician, but at least 20% present to secondary care as emergencies. Overall, 89% of cases were histo-cytologically confirmed with that figure appearing to rise slowly over the audit period from 81% (2006) to 92% (2011). Survival data is shown below.

      n (%) Median survival (days) 1 year survival (%)
      All patients 8,503 (100%) 278 41
      Survival was slightly better in females (median 304 days vs 274 days HR 0.91, p=0.002)
      Subtype n (%) Median survival (days) 1 year survival (%)
      Unspecified 3,798 276 39.5
      Epithelioid 2,300 388 53.2
      Sarcomatoid 439 123 16.4
      Biphasic 268 274 36.0
      37% of patients received no anti-cancer treatment, but 28%, 26% and 30% of patients received “surgery”, chemotherapy or radiotherapy at any time. Most surgical operations (60%) were pleurodesis. Median survival varied by first treatment modality: surgery 378 days, chemotherapy 399 days, radiotherapy 308 days, no anti-treatment 140 days. Survival was highest in patients having “surgery” and chemotherapy (491 days). Use of chemotherapy varied across 28 regional cancer networks from 14% to 41% of patients, but overall increased over the audit period from 13% to 34%.

      Conclusion
      Mesothelioma is predominantly a cancer of elderly males, with a striking tendency for right-sided disease. Only 11% have no histological confirmation, but where this is obtained, the epithelioid subtype has best prognosis. Low rates of anti-cancer treatment may reflect therapeutic nihilism as well as patient fitness, but there is an encouraging trend towards wider use of chemotherapy which was associated with a greater than doubling in survival compared with no treatment.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P2.14 - Poster Session 2 - Mesothelioma (ID 196)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Mesothelioma
    • Presentations: 1
    • +

      P2.14-014 - A Phase 2 Randomized, Double-blind, Placebo-Controlled, Multicenter Study of VS-6063 as Maintenance Therapy in Subjects with Malignant Pleural Mesothelioma which has Not Progressed on at least 4 Cycles of Pemetrexed/Platinum therapy (ID 3375)

      09:30 - 09:30  |  Author(s): D. Fennell

      • Abstract

      Background
      Malignant pleural mesothelioma (MPM) is an aggressive tumor in the pleural lining of the lung usually caused by asbestos exposure. Median OS following frontline chemotherapy with pemetrexed/cisplatin is ~12 months. There is no established second line therapy. Approximately 50% of MPM patients exhibit homozygous disruption of the NF2 tumor suppressor gene by mutation and/or deletion resulting in lack of expression of functional merlin protein. Preclinical data have indicated that mesothelioma cell lines that lack NF2/Merlin are especially sensitive to focal adhesion kinase (FAK) inhibition in both cellular and animal models. Interestingly, pemetrexed and cisplatin increase cancer stem cells (CSCs), while FAK inhibitors have been found to decrease CSCs in mesothelioma models. Given the sensitivity of mesothelioma cells lacking NF2/Merlin and the effect on CSCs, the use of a FAK inhibitor in a maintenance setting after first line chemotherapy may be an attractive strategy to extend survival of MPM patients. VS-6063 is an orally bioavailable selective inhibitor of FAK. In a phase 1 trial VS-6063 was generally well tolerated, with grade 1/2 nausea, vomiting and fatigue as the most frequent adverse events (Jones SF J Clin Oncol 2011 29:1 suppl; abstr 3002).

      Methods
      A multinational, randomized, double-blind, placebo controlled, phase 2 clinical trial was designed to determine if VS-6063 provides superior clinical benefit compared with placebo as a maintenance treatment in patients with MPM following frontline therapy with pemetrexed/platinum therapy. The study aims to assess whether VS-6063 improves median OS and median PFS over placebo. Randomization will be stratified by Merlin status (high versus low) and patients will receive either VS-6063 400mg BID continuously or matched placebo (1:1). The study follows an adaptive enrichment design where, pending results from an interim analysis, sampling may be restricted to patients with low Merlin protein expression if promising results are observed among the subpopulation. Approximately 370 eligible patients with pathologically confirmed MPM, who have PR or SD following at least 4 cycles of pemetrexed with either cisplatin or carboplatin, Karnofsky PS ≥70%, will be enrolled. Patients will continue treatment until disease progression. Archival tumor tissue will be used for the analysis of Merlin status and is therefore required for participation. Secondary endpoints include patient-reported outcomes of health-related quality of life and disease- or treatment-related symptoms utilizing the LCSS-meso scale, objective response and safety and tolerability. Clinical trial information: NCT01870609.

      Results
      not applicable

      Conclusion
      not applicable