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M. Mencoboni



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    MINI 24 - Epidemiology, Early Detection, Biology (ID 140)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
    • Presentations: 1
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      MINI24.13 - Molecular and Pathological Features of Different Malignant Pleural Mesothelioma (MPM) Histologic Subtypes (ID 2121)

      17:55 - 18:00  |  Author(s): M. Mencoboni

      • Abstract
      • Presentation
      • Slides

      Background:
      Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis and limited treatment options. Sarcomatoid/biphasic mesotheliomas are characterized by more aggressive behaviour, characterized by a higher resistance to systemic treatments, more frequent distant spread and a poorer prognosis compared with the epithelioid subtype. To date prognostic and tailored therapeutic biomarkers are lacking

      Methods:
      The present study analyzed the expression levels of MDM2 and HIF1alpha and the presence of inflammation, necrosis and proliferation in different histologic subtypes from chemonaive MPM patients. Diagnostic biopsies of MPM patients from four Italian cancer centers were centrally collected and analyzed. MDM2, and HIF1alpha expression levels were investigated through immunohistochemistry and RT-qPCR. A pathological assessment of necrosis, inflammation and proliferation index (through Ki67 immunostaining) was also performed. Molecular markers, pathological features and clinical characteristics were related to overall (OS) and progression free survival (PFS).

      Results:
      Sixty MPM patients were included in the study (32 epithelioid and 28 non-epithelioid). Higher levels of MDM2 (p<0.001), HIFalpha (p=0.013), necrosis (p=0.013) and proliferation index (p<0.001) were significantly associated with sarcomatoid/biphasic subtypes, while higher levels of inflammation were significantly associated with epithelioid subtype (p=0.044). MDM2 expression levels were correlated with HIF1alpha (p=0.0001), necrosis (p=0.008) and Ki67 (p=0.009). Univariate analysis showed a significant correlation of non-epithelioid histology (p=0.04), high levels of necrosis (p=0.037) and proliferation index (p=0.0002) with shorter PFS. This finding, however, was not confirmed by the multivariate analysis.

      Conclusion:
      Sarcomatoid/biphasic and epithelioid mesotheliomas show different MDM2 and HIF1alpha expression levels and are characterized by different levels of necrosis, proliferation and inflammation. Further studies are warranted in order to confirm a prognostic and predictive role of such markers and features.

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    P2.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 225)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
    • Presentations: 1
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      P2.08-005 - Vinorelbine as Second or Third-Line Therapy in Pemetrexed-Pretreated Malignant Pleural Mesothelioma (MPM) Patients (ID 2403)

      09:30 - 09:30  |  Author(s): M. Mencoboni

      • Abstract

      Background:
      There is no standard treatment for patients (pts) with MPM progressing during or after pemetrexed/platinum-based chemotherapy (PBC). Single agent chemotherapy is often administered in everyday practice, although its use is poorly supported by clinical trials. The aim of this retrospective study (NCI01865045) was to analyze the efficacy and toxicity of second (2nd) and third (3rd) line vinorelbine (VNR) in a large cohort of PBC-pretreated MPM patients.

      Methods:
      The clinical records of MPM pts consecutively treated in 8 Italian Centers with intravenous (iv) or oral (po) VNR as 2nd or 3rd line treatment following PBC were reviewed. Radiological response was assessed by modified RECIST criteria. Toxicity was reported according to CTCAEv4 criteria. Relative dose-intensity (DI) of VNR was calculated. Progression-free survival (PFS) and overall survival (OS) were estimated and correlated to clinical variables: age, gender, histological subtype, ECOG performance status (PS), line of VNR therapy (2nd vs 3rd) and outcome of first-line treatment.

      Results:
      From August 2001 to September 2014, 161 pts (M/F 120/41) were treated, 128 with iv and 33 with po VNR. Most of the cases included (92%) were treated after 2007. Histological subtype was epithelioid in 134, biphasic in 15, sarcomatoid in 8 and unspecified in 4 pts. Median age was 67 years (range 41-82). VNR was administered as 2nd or 3rd line treatment in 94 and 67 pts, respectively. Median number of VNR cycles was 3 (range 1-26), median relative DI was 88%. Main grade 3-4 toxicities were neutropenia in 9%, fatigue in 4% and constipation in 5% of pts. No toxic death occurred. A partial response was observed in 10 pts (6%), stable disease in 57 (35%), for an overall disease control rate of 41%. Median PFS and OS were 2.5 and 6.7 months, respectively. In multivariate analysis, only ECOG PS (0 vs 1-2) was significantly associated with improved PFS and OS. An analysis of molecular predictors of VNR response is ongoing.

      Conclusion:
      In this large retrospective patient cohort, 2nd and 3rd line VNR had modest but definite activity in PBC-pretreated MPM patients, with an excellent toxicity profile. Although inclusion in prospective clinical trials of new agents should be always considered in this setting, single agent VNR remains a reasonable option for palliation.