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Maurizio Infante



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    MA25 - Oligometastasis: Defining, Treating, and Evaluating (ID 929)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Oligometastatic NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 13:30 - 15:00, Room 203 BD
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      MA25.02 - Searching for a Definition of Synchronous Oligometastatic (sOMD)-NSCLC: A Consensus from Thoracic Oncology Experts (ID 13452)

      13:40 - 13:45  |  Author(s): Maurizio Infante

      • Abstract
      • Presentation
      • Slides

      Background

      Recent prospective single centre studies reported improved outcomes in patients with sOMD-NSCLC who were treated with radical intent. Since then sOMD has been perceived as a separate disease entity. However, a clear definition of sOMD-NSCLC is lacking. We aimed to develop a definition and diagnostic criteria of sOMD-NSCLC following a consensus process.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A European multidisciplinary consensus group was established with representatives from different scientific societies. Consensus questions were extracted from a survey, case series and a systematic review. The questions were discussed, and the statement formulated during a consensus meeting in Dublin (23.01.18).

      4c3880bb027f159e801041b1021e88e8 Result

      Summary of consensus statement

      Defining sOMD-NSCLC

      Definition of sOMD is relevant for patients in whom a radical treatment is technically feasible with acceptable toxicity, taking into account all sites, that may modify the course of the disease leading to a long-term disease control.

      All sites must be technically and safely treatable.

      The maximum number of metastases/organs meeting the criteria involved will depend on the possibility of offering a treatment strategy with radical intent, taking into account local control and toxicity. Based on the systematic review, a maximum of 5 metastases and 3 organs is proposed.

      Diffuse serosal metastases and bone marrow involvement are excluded.

      Mediastinal lymph node (MLN) involvement should be considered as locoregional disease in the definition of sOMD-NSCLC.

      MLN involvement is of importance in determining if a radical local treatment of the primary tumour may be applied and the MLN will not be counted as a metastatic site.

      Staging of sOMD-NSCLC

      PET-CT and brain imaging are considered mandatory.

      In case of a solitary liver metastasis a dedicated MRI of the liver and for a solitary pleural metastasis, thoracoscopy and biopsies of distant ipsilateral pleural sites are advised.

      Staging of the mediastinum requires a minimum of a FDG-PET scan, with pathological confirmation preferred if this influences the treatment strategy.

      Pathological proof is required unless the MDT decides that the risk outweighs the benefit. Pathology proof is advised for single metastatic location and if it may change the therapeutic strategy, confirmation of the MLN involvement is recommended.

      8eea62084ca7e541d918e823422bd82e Conclusion

      A multidisciplinary consensus statement on the definition and staging of sOMD-NSCLC was formulated taking into account results of a European survey, a systematic review and case discussion. This statement might be helpful to standardise inclusion criteria in future clinical trials. However, the definition of sOMD may change over time when more prospective data will become available.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.04 - Immunooncology (Not CME Accredited Session) (ID 953)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.04-12 - A Genomic Signature [JAK2, JAK3, PIAS4, PTPN2, STAT3, IFNAR2] Predicts Baseline Resistance to Nivolumab in Advanced NSCLC. (ID 13459)

      16:45 - 18:00  |  Author(s): Maurizio Infante

      • Abstract
      • Slides

      Background

      With the exception of PD-L1 expression for pembrolizumab, no biomarkers allow to maximize the benefit of immunotherapy in advanced pretreated non-small-cell lung cancer (AP-NSCLC). The genomic abnormalities of genes involved in immune-escape/editing are suggested as baseline mechanisms of resistance.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A retrospective series of AP-NSCLC patients (pts) undergone Nivolumab (NIVO) was collected. FFPE-tumor blocks were analyzed to identity somatic mutations (SMs)/ copy number variations (CNVs) with a Ampliseq CGS panel (17 genes: APLNR, B2M, IFNAR1, IFNAR2, IFNGR1, IFNGR2, IRF9, JAK1, JAK2, JAK3, PIAS4, PTPN2, SOCS1, STAT1, STAT2, STAT3 and TYK2). End-points were overall-, progression-free-survival (OS/PFS) and objective response rate (ORR).

      4c3880bb027f159e801041b1021e88e8 Result

      Data from 24 consecutive AP-NSCLC pts who received NIVO were gathered (median age 69.5 yrs, median number of previous lines 3 [2-5], 2nd line NIVO [70.8%], median follow-up 6.8 months [range 1-23], deaths 14 [58.3%], male/female 79.2/20.8%, squamous/non-squamous 41.7/58.3%, EGFR mutant 5 [20.8%]). ORR (partial) was obtained in 4 pts (16.6%, 95% CI 1.7-31.6%), with stable- and progressive-disease in 5 (20.8%, 95% CI 4.5-37.1%) and 15 (62.5, 95% CI 43.1-81.8%) pts, respectively. JAK3/JAK2 (6/3 pts, 25/12.5%) CNVs, and IFNAR2/STAT3 SMs (2 pts, 8.3%) were the most frequent (>1 pts) abnormalities. The 12 pts with JAK3, PIAS4, PTPN2, STAT3, IFNAR2 and JAK2/3 SMs/CNVs had a significantly lower median OS (4 months, 95% CI 1-8) and PFS (3 months, 95% CI 2-3.5) than the other 12 pts wild-type/other alterations (median OS 13 months, n.e.; median PFS 6 months 95% CI 5-9) [p=0.046 for OS, p=0.002 for PFS]. No objective responses were observed in the pts’ subgroup harboring the gene signature (p=0.09). At multivariate analysis, the genomic signature was independently associated with shorter OS (HR 2.20 95% CI 1.21-4.06, p=0.01) and PFS (HR 6.1 95% CI 2-18.7, p=0.001). No significant correlation between EGFR mutations and outcome was found.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Despite the small sample, the customized gene sequencing of few genes involved in immune-escape/editing is able to identify a pts’ subgroup of AP-NSCLC who appears to derive a lower benefit from NIVO, supporting intrinsic resistance. A larger prospective validation is planned.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P3.08 - Oligometastatic NSCLC (Not CME Accredited Session) (ID 974)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.08-04 - OMEGA, A Randomized Trial of Local Ablative Therapy Vs. Conventional Treatment in Oligometastatic NSCLC – Trial in Progress (ID 13971)

      12:00 - 13:30  |  Presenting Author(s): Maurizio Infante

      • Abstract
      • Slides

      Background

      A recent randomized phase 2 study has shown that local ablative therapy in addition to systemic treatment was superior to maintenance therapy in prolonging disease-free survival in NSCLC patients harboring up to three metastatic sites.

      Oligometastatic lung cancer (OM-NSCLC) seems thus to be associated with a better prognosis than usual Stage IV non-small cell lung cancer when radical local therapy of all metastatic sites is administered but the impact of such an approach on overall survival and quality of life remains unclear

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A consortium of tertiary referral centres involved in Lung Cancer management at the national level was established with the aim of setting up a randomized trial addressing this issue

      4c3880bb027f159e801041b1021e88e8 Result

      A randomized trial of local ablative therapy in OM-NSCLC patients with potentially resectable or locally controlled primary tumors has been designed and 7 tertiary referral centers agreed to participate

      Patients with synchronous or metachronous oligometastatic lung cancer (1-3 metastatic lesions) will be randomized to local ablative therapy + standard treatment Vs. standard treatment.

      Balancing between study arms will be performed according to synchronous vs. metachronous presentation, Number of oligometastases, Nodal status and Oncogene-addiction or PDL-1 expression.

      Primary outcome will be Overall Survival (OS) from randomization. The sample size is set to 195 patients.

      Inclusion criteria include adequate performance status, primary tumor controlled or controllable staging with whole-body FDG PET scan and brain MRI, fit to receive at least 3 cycles of platinum-based doublet chemotherapy, or immunotherapy or targeted agents according to molecular profile.

      Exclusion criteria include cerebral oligometastasis alone (will receive local therapy in any case),

      metastasis in sites where normal radiotherapy constraints cannot be met, multiple subsolid nodules in the absence of extrapulmonary metastasis, prior malignant tumor with some exceptions, relevant co-morbidities that would significantly reduce life expectancy on their own,

      Disease state and life status assessed on a 2-monthly basis by physical examination, whole-body CT scan plus repeat PET-scan if needed and Brain MRI if brain metastasis at enrolment. Toxicity and adverse events will be assessed according to NCI-Common Terminology Criteria. Quality of life will be assessed at randomization and after six months by the SF36/LCSS.

      8eea62084ca7e541d918e823422bd82e Conclusion

      There is a clear need for randomized controlled trials with overall survival as their main endpoint to confirm whether local ablative therapy indeed has a role in the management of oligometastatic lung cancer. The Omega trial will try to respond to such a need.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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