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Anna F. Farago



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    MS32 - SCLC - From Benchside to Bedside - Clinical Science Session (ID 810)

    • Event: WCLC 2018
    • Type: Mini Symposium
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 13:30 - 15:00, Room 107
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      MS32.02 - Patient Derived Models (PDX & CTC-Derived) (ID 11541)

      13:45 - 14:00  |  Presenting Author(s): Anna F. Farago

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    P1.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 944)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.12-17 - Overall Survival and Recurrence After Surgical Resection of Pure and Mixed Large Cell Neuroendocrine Tumors. (ID 13051)

      16:45 - 18:00  |  Author(s): Anna F. Farago

      • Abstract
      • Slides

      Background

      Large-cell neuroendocrine carcinoma (LCNC) is an aggressive tumor with poor prognosis and undefined treatment. We performed a retrospective analysis on the outcomes of surgical resection and adjuvant therapy to assess the effectiveness of treatment.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Retrospective review of patients with LCNC who underwent surgical resection at a single-center tertiary care facility from 2002-2017. Survival times were assessed from day of surgery until death. A Kaplan-Meier method for overall survival (OS) and for recurrence was used and compared across prognostic factors using log-rank analysis and a Cox proportional hazard model.

      4c3880bb027f159e801041b1021e88e8 Result

      Sixty-two patients were identified with a median follow up of 3.4 years. Of these, 26 (41.9%) were male and 56 (90.3%) were current or former smokers. The majority of patients underwent a lobectomy/segmentectomy (72.6%), while a smaller percentage (14.5%) underwent wedge resection, and the remainder pneumonectomy or bi-lobectomy (4.8%). Pathologically, 31 (54.4%) were stage I, 20 (35.1%) stage II, and 6 (10.5%) stage III-IV. Additionally, 35 (56.4%) represented pure LCNC while the remaining 27 (43.6%) had a mixed histology. Median OS for resected stage I disease was 11.3 years, decreased to 4.4 years in stage II disease, and was 0.8 years in stage III-IV disease (p = 0.01) (Figure 1). For those that recurred, median time to recurrence was 1.20 years for stage I and 1.15 years for stage II disease. Adjuvant therapy, type of resection, and tumor histology (pure vs. mixed) had no significant impact on OS on unadjusted or adjusted analysis.

      figure1.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      LCNC is associated with early recurrence after surgical resection and poor survival for patients with stage III and IV disease. In patients with mixed histology survival and recurrence remain similar to those with pure LCNC tumors.

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    P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.13-40 - Rapid, Robust and Durable Responses to Larotrectinib in Patients with TRK Fusion Non-Small Cell Lung Cancer (ID 14528)

      16:45 - 18:00  |  Presenting Author(s): Anna F. Farago

      • Abstract
      • Slides

      Background
      Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic independent of tumor lineage and are widely distributed across cancers. NTRK gene fusions were first reported in lung cancer in 2013 (Vaishnavi et al Nat Med 2013). Larotrectinib is a potent and highly selective oral tropomyosin receptor kinase (TRK) inhibitor in clinical development. Initial data of treatment of 55 patients with TRK fusion cancer resulted in an investigator-assessed objective response rate of 80%, and 71% of patients still in response at one year (Drilon et al., NEJM 2018). We report here on the safety and efficacy of larotrectinib in 4 patients with NSCLC from the 55 patient dataset.
      a9ded1e5ce5d75814730bb4caaf49419 Method
      Patients with previously treated lung adenocarcinoma were treated under clinical trial and enrolled based on a molecular report of NTRK gene fusion from a CLIA-certified lab. Larotrectinib was administered at 100 mg BID until disease progression or lack of clinical benefit. Tumors were assessed by investigators every 8 weeks using RECIST v1.1 criteria.
      4c3880bb027f159e801041b1021e88e8 Result

      As of July 17, 2017, four patients with adenocarcinoma of the lung who had progressed after 1 or more lines of platinum-based chemotherapy for advanced disease were enrolled. Three patients harbored an NTRK1 fusion and one an NTRK3 fusion. Three of 4 patients had a partial response or complete response confirmed on a subsequent scan. One patient with a possible brain metastasis demonstrated regression of mass on MRI. Responses were rapid and robust, with a time to response ranging between 49 and 56 days. At the time of analysis, 3 patients continued to have an ongoing response ranging between 5.7 and 12 months. The other patient had stable disease and progressed outside of the CNS after 300 days of treatment and continued on larotrectinib for clinical benefit. Larotrectinib was well tolerated, with 3 of 4 patients having grade 1 events only.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Larotrectinib treatment resulted in rapid and durable responses and had a well tolerated adverse event profile with no CNS progressive events in patients with previously treated lung cancer harboring NTRK gene fusions. These results strongly support the inclusion of NTRK gene fusions as part of routine testing for patients with lung cancer.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P3.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 978)

    • 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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      P3.12-02 - Dynamics of DLL3 and ASCL1 Expression in SCLC Over Disease Course (ID 12609)

      12:00 - 13:30  |  Presenting Author(s): Anna F. Farago

      • Abstract
      • Slides

      Background

      SCLC is a high-grade neuroendocrine malignancy highly responsive to first-line therapy, etoposide plus platinum (EP), but increasingly resistant to subsequent lines of therapy. Because SCLC is rarely biopsied following the initial diagnosis, the dynamics of expression of therapeutically relevant biomarkers in relapsed disease are poorly understood. ASCL1 is an oncogenic driver of SCLC and directs transcription of delta-like protein 3 (DLL3), an atypical Notch receptor family ligand involved in neuroendocrine tumorigenesis and the target of the antibody drug conjugate rovalpituzumab tesirine (Rova-T™). We investigated ASCL1 and DLL3 expression in SCLC patient (pt) tumor biopsies and patient-derived xenografts (PDXs) collected serially from time of diagnosis (pre-treatment) and after progression following ≥1 lines of therapy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Fresh cut, formalin fixed, paraffin embedded tissue from primary SCLC tumors and PDXs was sectioned and stained with mouse monoclonal antibodies against DLL3 (SC16.65) and ASCL1 (SC72.201) on the Dako platform. ASCL1 and DLL3 expression were scored as a percent of positive cells and correlated with each pt’s treatment history.

      4c3880bb027f159e801041b1021e88e8 Result

      Among biopsies and/or PDXs derived over serial time points, 6 cases had baseline positive DLL3 expression ranging from 15-80% of cells with a mean of 50% pre-EP. All 6 remained positive following progression after EP, with DLL3 expression ranging from 10-100% of cells with a mean of 66%. Up to 7 serial tissue or PDX samples were available over the course of multiple treatments for 2 pts, and DLL3 and ASCL1 expression remained consistent over time, being strongly positive in 1 case and negative in the other. Among biopsies and PDXs established at matched time points, ASCL1 and DLL3 expression were consistent in 7/7 and 7/8 cases, respectively.

      8eea62084ca7e541d918e823422bd82e Conclusion

      ASCL1 and DLL3 expression remain mostly consistent pre- and post- chemotherapy in pts with SCLC, suggesting that expression of these biomarkers in archival tissue likely accurately estimates expression even after intervening treatments. Furthermore, PDXs derived both from biopsies and circulating tumor cells maintain ASCL1 and DLL3 expression that reflects the pt tumor, supporting use of PDXs to model pt tumor biology.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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