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Aaron S. Mansfield



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    EP1.12 - Small Cell Lung Cancer/NET (ID 202)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.12-06 - New Treatment Option for ES-SCLC: Patient Characteristics and Use of an Atezolizumab Regimen in the Real-World Setting (Now Available) (ID 2651)

      08:00 - 18:00  |  Author(s): Aaron S. Mansfield

      • Abstract
      • Slides

      Background

      Results from the Phase III IMpower133 study (NCT02763579) were previously made public. Based on improvements in overall survival in patients with extensive-stage small cell lung cancer (ES-SCLC) who received atezolizumab plus carboplatin and etoposide (IMpower133 regimen) vs chemotherapy administered in the 1L setting, the NCCN added this regimen to its guidelines (category 1, preferred) on October 10, 2018. Accordingly, some providers began implementing this regimen in their clinical practice, creating a unique opportunity to characterise its early and broad use in a real-world setting.

      Method

      Patients with ES-SCLC who started treatment within 90 days of initial diagnosis and had a confirmed administration of atezolizumab with carboplatin or cisplatin and etoposide (atezo regimen) on or after September 25, 2018, were included from the de-identified Flatiron Health electronic health records–derived database, representing > 280 US cancer clinics (≈ 800 sites of care). Treatment data were analysed through April 30, 2019. Broad use was defined as treatment with the atezo regimen outside of several main clinical trial restrictions (ECOG PS ≥ 2, abnormal laboratory values, cisplatin use or as 2L treatment). Frequencies and percentages are reported. Monthly uptake was defined as the percentage of ES-SCLC patients starting 1L therapy each month who were treated with the atezo regimen.

      Result

      Uptake of the atezo regimen increased from 10% in October 2018 to 46% in February 2019 (before FDA approval on March 18, 2019) and 66% in April 2019 (after FDA approval); 143 patients were identified, 92% of whom had ES-SCLC at initial diagnosis (Table). The atezo regimen was used broadly among 46% of patients (18% with ECOG PS ≥ 2, 18% with an abnormal laboratory value, 1% on cisplatin, 17% as 2L ES-SCLC treatment). The median time from ES-SCLC diagnosis to start of the atezo regimen was 16 days for 1L patients and 78 days for 2L patients. Patients treated with the atezo regimen in the 1L were administered atezolizumab at a median of 8 days after start of chemotherapy; those treated in the 2L were typically administered atezolizumab immediately at the start of the line.

      Conclusion

      This real-world analysis demonstrates the broad use of the atezo regimen, with nearly half of patients treated outside of several main IMpower133 trial restrictions. Further, a rapid uptake of the regimen even before FDA approval underscores its impact on changing clinical practice and the high unmet need of this patient population.

      Table. Characteristics of Patients Treated With the Atezolizumab Plus Carboplatin/Cisplatin and Etoposide Regimen in Routine Clinical Care

      Patients, n

      143

      Treated prior to FDA approval (March 18, 2019), n (%)

      101 (71)

      Median age at ES-SCLC diagnosis (IQR), years

      67 (61, 73)

      Aged ≥ 65 years at ES-SCLC diagnosis, n (%)

      90 (63)

      Female, n (%)

      71 (50)

      White, n (%)

      100 (70)

      Smoking history, n (%)

      137 (96)

      Stage at initial diagnosis, n (%)

      LS

      7 (5)

      ES

      132 (92)

      Unknown

      4 (3)

      ECOG PS, n (%)a

      0 or 1

      76 (53)

      2+

      26 (18)

      Unknown

      41 (29)

      Radiation therapy, n (%)b

      14 (10)

      LS setting, n

      7

      ES setting, n

      7

      Regimen, n (%)

      Atezolizumab, carboplatin, etoposide

      141 (99)

      Atezolizumab, cisplatin, etoposide

      2 (1)

      Line of therapy of atezo regimen in ES setting, n (%)

      1L

      119 (83)

      2L

      24 (17)

      Median time from ES-SCLC diagnosis to start of line of therapy containing atezo regimen (IQR), days

      1L

      16 (11, 26)

      2L

      78 (59, 98)

      Median time from ES-SCLC diagnosis to first administration of atezo within line (IQR), days

      1L

      24 (14, 27)

      2L

      78 (59, 98)

      Abnormal baseline laboratory value, n (%)c

      26 (18)

      1L, first line; 2L, second line; atezo, atezolizumab; ECOG, Eastern Cooperative Oncology Group; FDA, US Food and Drug Administration; IQR, interquartile range; LS, limited stage; PS, performance status.

      a ECOG PS value closest to within −30 to +7 days of treatment start.

      b Includes radiation therapy to chest following initial diagnosis of SCLC, including concurrent radiation therapy with systemic chemotherapy, chemotherapy followed by radiation therapy, up-front palliative radiation therapy to the chest or for superior vena cava syndrome.

      c Abnormal values defined as those not meeting the following definitions: absolute lymphocyte count ≥ 500/μL, lymphocyte count ≥ 500/μL, absolute neutrophil count ≥ 1500 cells/μL, platelet count ≥ 100,000/μL, hemoglobin ≥ 9.0 g/dL, aspartate aminotransferase ≤ 5 × upper limit of normal (ULN), alanine aminotransferase ≤ 5 × ULN, alkaline phosphatase ≤ 5 × ULN, serum bilirubin ≤ 1.25 × ULN, serum creatinine ≤ 1.5 × ULN, serum calcium ≤ 12 mg/dL.

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    EP1.15 - Thymoma/Other Thoracic Malignancies (ID 205)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Thymoma/Other Thoracic Malignancies
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.15-08 - Association of Perioperative Chemotherapy with Survival in Thymic Malignancies (ID 1436)

      08:00 - 18:00  |  Author(s): Aaron S. Mansfield

      • Abstract
      • Slides

      Background

      Patterns of perioperative chemotherapy utilization and its association with survival in thymic malignancies are largely unknown.

      Method

      We queried NCDB from years 2004-2014 and identified 3,788 patients with non-metastatic thymic carcinoma (TC) and thymoma who received surgery. We compared patients who received perioperative chemotherapy to those who didn't and used a Cox proportional hazards model to determine predictors of mortality.

      Result

      764 patients (20%) received chemotherapy: 287(38%) neoadjuvant (NAC), 347(45%) adjuvant (AC), and 130(17%) unspecified. 184(24%) had TC; the rest had thymoma. Patients who didn’t receive chemotherapy (N=3024) had older age (median 62 vs 47, P<0.01) and earlier stage (51% versus 24% stage I-IIA, P<0.01). In multivariable analysis, patients who received AC versus no chemotherapy had a similar overall survival(OS); however, NAC predicted a worse OS. For separate thymoma and TC subsets, median OS did not differ between those who received AC and those who didn’t in either group. AC did not improve OS for patients with R1/R2 margins (114 months, 95%CI 94-NR vs 131 months, 95%CI 118-NR)

      Characteristic

      Hazard ratio for mortality (95% confidence interval) 1

      Age

      1.03 (1.03-1.04)

      Thymoma vs. TC

      0.50 (0.43-0.58)

      Charlson-Deyo score>0

      1.40 (1.21-1.63)

      Chemotherapy

      None

      Adjuvant

      Neoadjuvant

      Unclassified

      1

      1.13 (0.89-1.44)

      1.77 (1.37-2.27)

      1.60 (1.16-2.19)

      Masaoka-Koga Stage

      I-IIA

      IIB

      III

      Unknown/other

      1

      1.08 (0.88-1.34)

      1.59 (1.34-1.90)

      2.71 (2.01-3.65)

      Radiation

      0.78 (0.67-0.91)

      Positive margin

      1.55 (1.33-1.81)

      1Model included sex, academic center, insurance, and race/ethnicity

      tc_surv_plot_stages_chemo_thymic_carcinoma.jpg

      tc_surv_plot_stages_chemo_thymoma.jpg

      Conclusion

      Chemotherapy in the perioperative setting was not associated with improved OS in either TC or thymoma. Prospective controlled studies are needed to determine the role of perioperative chemotherapy in thymic malignancies.

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    ES17 - Molecular Alterations and Heterogeneity in Mesothelioma (ID 20)

    • Event: WCLC 2019
    • Type: Educational Session
    • Track: Mesothelioma
    • Presentations: 1
    • Now Available
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      ES17.03 - Heterogeneity &amp; Immune Checkpoint Expression (Now Available) (ID 3249)

      11:00 - 12:30  |  Presenting Author(s): Aaron S. Mansfield

      • Abstract
      • Presentation
      • Slides

      Abstract

      Mesothelioma is a spatially complex malignancy. Morphologic heterogeneity is commonly identified, especially with surgical resection that can unmask distinct histologic components across sites of disease. Molecular analyses of HUMARA methylation patterns on the X-chromosome, CDKN2A deletions, and single nucleotide variants from multiple tumor sites all suggest that mesothelioma is polyclonal with multiple genetic subclones within each tumor. Temporal histologic heterogeneity has also been reported with sarcomatoid differentiation during progression of disease. The selective pressures of the microenvironment and therapies may further drive tumor heterogeneity. With the application of immune checkpoint inhibitors for the treatment of this disease, the expression of immune checkpoints and the immunologic milieu of mesothelioma has been increasingly investigated. Whereas most studies report immune checkpoint expression from a single site of disease obtained from a single time point, distinct immunologic patterns have been observed within tumors from different sites. The molecular and immunologic heterogeneity of mesothelioma may have prognostic and therapeutic implications.

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    MA23 - Preclinical Models and Genetics of Malignant Pleural Mesothelioma (ID 353)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Mesothelioma
    • Presentations: 1
    • Now Available
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      MA23.07 - Loss of Expression of BAP1 and/or MTAP Aids in the Diagnosis of Malignant Mesothelioma Metastatic to Lymph Nodes (Now Available) (ID 1121)

      14:30 - 16:00  |  Author(s): Aaron S. Mansfield

      • Abstract
      • Presentation
      • Slides

      Background

      Stage and histology are the strongest prognostic parameters in malignant pleural mesothelioma and aid management of patients. However, the distinction between reactive intranodal mesothelial cells and metastatic malignant mesothelioma (MM) can be challenging. Loss of BRCA1 associated protein-1 (BAP1) and/or methylthioadenosine phosphorylase (MTAP) expression has been identified in a subset of MM but not in reactive mesothelial proliferation. We investigated the value of these markers in the distinction between reactive mesothelial cells and metastatic MM in lymph nodes.

      Method

      Surgical files of Mayo Clinic Rochester (1996-2018) were searched for metastatic MM in lymph nodes. All cases and if available corresponding primary MM were reviewed by a thoracic pathologist (ACR) to confirm the diagnosis. Primary MM and lymph nodes were stained with BAP1 (clone C-4) and MTAP (2G4). Absence of nuclear staining of BAP1 and absence of nuclear and cytoplasmic staining of MTAP in essentially all tumor cells was considered as loss of expression.

      Result

      Forty-four patients (25 males, 56.8%) had a median age of 64 years (range, 24-75) at time of surgery. Tissue was available from nodal metastases in all cases, either paired with the primary MM at time of nodal sampling (N=37) or at a different time (N=4) (time between tissue collections, range, 1day- 4 years, respectively), or without paired primary MM (N=3). Thirty-seven pleural, 6 peritoneal and 1 pericardial MM were of epithelioid (N=39) or biphasic (N=5) subtype. Patients underwent extrapleural pneumonectomy (N=17), pleurectomy (N=7), resection (N=9), debulking (N=2), biopsy (N=8), or autopsy (N=1). In nodal metastases, BAP1 and/or MTAP expression was lost in 29 (of 43, 67.4%) cases; specifically, BAP1 expression was lost in 28 (of 44, 63.6%), MTAP was lost in 14 (of 43, 32.6%), and both were lost in 12 (of 43, 27.9%) cases. Agreement in expression/loss of expression of BAP1 and/or MTAP in primary and metastatic MM occurred in all cases. During a median follow up of patients who underwent extrapleural pneumonectomy or pleurectomy (available in N=23) of 14.8 months (range, 1-119) 17 patients died within a median time of 16 months.

      Conclusion

      BAP1 and MTAP immunostains are helpful in the distinction between metastatic MM and reactive mesothelial cells in lymph nodes when one or both markers lost expression in the mesothelial cells. Expression of both markers does not exclude the possibility of metastatic MM.

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    OA02 - A New Vision of Targets and Strategies (ID 120)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
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      OA02.05 - First-In-Human Phase 1/2 Trial of Anti-AXL Antibody–Drug Conjugate (ADC) Enapotamab Vedotin (EnaV) in Advanced NSCLC (Now Available) (ID 343)

      10:30 - 12:00  |  Author(s): Aaron S. Mansfield

      • Abstract
      • Presentation
      • Slides

      Background

      AXL, a transmembrane receptor tyrosine kinase, is aberrantly expressed in various cancers, and associated with poor prognosis and treatment resistance. AXL overexpression is associated with resistance to PD-1 immune checkpoint inhibitors (Hugo et al. 2016). EnaV, a novel ADC of anti-AXL human IgG1 and monomethyl auristatin E, demonstrated potent anti-tumor activity in preclinical models, including NSCLC (Boshuizen et al. 2018). In a phase 1, dose escalation, multi-cohort trial (NCT02988817) in heavily pretreated patients with relapsed or refractory solid tumors, EnaV 2.2 mg/kg once every 3 weeks (1Q3W; recommended phase 2 dose) showed preliminary anti-tumor activity. Here we present initial results from patients with NSCLC in the phase 2a, expansion phase of this trial.

      Method

      We analyzed data from EnaV 2.2 mg/kg 1Q3W, in the cohort of pretreated patients with stage III/IV NSCLC without sensitizing EGFR mutations (EGFR WT) or ALK rearrangements (ALK-) who had failed ≤4 prior lines of therapy, including platinum-based chemotherapy and PD-1/PD-L1 inhibitor (either in combination or sequentially). Endpoints include safety, objective response rate (ORR; RECIST 1.1), and AXL expression in fresh tumor biopsies (immunohistochemistry).

      Result

      In the EGFR WT/ALK- cohort, 26 patients (median age 65.5 years, range 38–74; 57.7% male) with ECOG PS of 0 (11.5%) or 1 (88.5%) have been enrolled. Most patients (23/26) were treated with a checkpoint inhibitor. At a median follow-up of 18 weeks (range: 2–54), the most common (≥20%; any grade) treatment-emergent adverse events (TEAEs) were fatigue, constipation, nausea, decreased appetite, decreased weight, diarrhea, and vomiting. Two patients had a TEAE leading to dose reduction. Grade ≥3 TEAEs occurred in 12 patients, with the most common being gastrointestinal disorders in eight patients (constipation [n=1]; colitis, diarrhea, nausea, vomiting [n=2 each]; abdominal distension [n=1]. The confirmed ORR is 19% (95% CI: 8.5%, 37.9%). The disease control rate (CR+PR+SD) is 50% (13/26). Nine of 12 (75%) evaluable fresh biopsies were positive for AXL tumor cell staining.

      Conclusion

      In this high unmet need patient population, with advanced EGFR WT and ALK- NSCLC who are pretreated with PD-1/PD-L1 inhibitors and platimum-based therapies, EnaV monotherapy demonstrated a manageable safety profile and encouraging preliminary clinical activity. This cohort has expanded to allow up to 60 patients to gain further knowledge of AXL as a potential biomarker for responsiveness to EnaV and to gather additional data on safety and efficacy. Funding: Genmab A/S

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    P1.01 - Advanced NSCLC (ID 158)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.01-45 - A NGS-Based ctDNA Test to Monitor Disease Progression and Treatment Response in Advanced Stage Non-Small Cell Lung Cancer (ID 3012)

      09:45 - 18:00  |  Author(s): Aaron S. Mansfield

      • Abstract

      Background

      The gold standard for clinical monitoring of lung cancer is CT imagining which is subjective and insensitive requiring a minimal of 2-3 months between repeat scans to be meaningful. As such, there is an urgent need to develop tests that can monitor anticancer treatment response and disease progression in real time. In this study, we evaluted the use of Next Generation Sequencing (NGS) for tumor associated genetic changes in circulating tumor DNA (ctDNA) to identify tumor mutations and the frequency of mutations detected in cfDNA to track tumor progression. We compared the results of a plasma based multigene mutation detection assay in advanced stage lung cancer patients to that of the routine CT scan and clinical observations.

      Method

      EDTA whole blood were prospecitvely collected within 48 hours of the CT scan and during the course of patients' clinical treatment. Platelet poor plasma were collected within 6 hours of the blood draw and stored at -80oC until use. In total, we accrued 121 plasma samples from 46 consented patients with advanced stage lung cancer and undergoing therapy at Mayo Clinic in Rochester, Minnesota. All data are stored in a RAVE databased and RECIST criteria were reviewed individually by an attending oncologist. NGS analysis were performed using a modified PlasmaSelect-R™ (Personal Genome Diagnostics, Maryland) assay to assess mutation type and fraction of ctDNA in plasma sample from each patient. The results were compared with CT scans at the time of each blood draw for their ability to 1) detect the cancer based on tumor associated mutations and 2) correlate with the clinical status (RECIST) of the disease based on the fraction of ctDNA in plasma.

      Result

      Among 121 plasma samples tested from 46 unique patients, 29 patients had three blood draws and 17 had a base line plus a follow up blood draw available for evaluation. More than 20 different tumor related mutations were observed. The number of mutations in each plasma sample ranged from 0 in eight patients to 5 in two individuals with allele frequencies ranging from 0.07% for TP53 gene mutation to 29% in the KRAS gene. Tumor associated mutations were detected in approximately 70% of the plasma samples. In a pilot set of 10 cases with baseline and one follow up blood draw, those with progression of disease (PD, n=4) had tumor associated mutations detected in both baseline and follow up blood draws. In contrast, the remaining six patients with stable disease (SD) or partical response (PR) by RECIST had zero or fewer mutations at follow up.

      Conclusion

      Our results suggestst that a liquid biopsy approach is highly feasible and very promising in clinical settings. For patients whose tumors carry a mutation, the use of liquid biopsy to monitor treatment response and disease progression reduces patients’ exposure to unnecessary radiation for surveillance of recurrent disease and enables a more sensitive and real-time monitoring of patients’ clinical status to guide further thearpeutic decisions. Complete mutational analysis with detailed clinical responses of each patients will be reported at the time of conference.

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    P1.06 - Mesothelioma (ID 169)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Mesothelioma
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.06-02 - National Trends in Outcomes in Patients with Malignant Pleural Mesothelioma (ID 1944)

      09:45 - 18:00  |  Author(s): Aaron S. Mansfield

      • Abstract

      Background

      Malignant pleural mesothelioma is an aggressive tumor and is often incurable. We aim to identify national practice patterns and trends in survival in patients with mesothelioma.

      Method

      We queried National Cancer Database from years 2004-2014 to identify adult mesothelioma cases. We collected baseline characteristics were collected and analyzed treatment patterns and survival trends. Multivariable Cox regression models were applied to identify factors associated with survival.

      Result

      Of 11,372 patients 4354 (38%) had epithelioid histology, 1431 (12%) sarcomatoid, 880 (0.7%) biphasic, and 4707 (41%) unspecified. 20% were stage IA, 22% stage IB, 2% stage II, 1% stage IIIA, 31% stage IIIV, and 23% were stage IV. Sarcomatoid histology was associated with worst overall survival (HR 2.2) while epithelioid histology had best survival (referent). Chemotherapy alone was the most common treatment modality (36%). Combined treatment with surgery, radiation, and chemotherapy was associated with best overall survival (HR 0.45) followed by chemotherapy combined with surgery. However, 1 year and 5-year OS remain low at 41.2% and 6.5% respectively. There has been no clinically significant improvement in overall survival from 2004 to 2014.

      Multivariate Cox Regression

      Variable

      Level

      HR (95% CI)

      Age

      Unit=1

      1.018 (1.015-1.020)

      Academic

      No vs Yes

      1.171 (1.124-1.221)

      Charlson Score

      1 vs 0

      1.104 (1.053-1.158)

      2 vs 0

      1.201 (1.109-1.300)

      >=3 vs 0

      1.460 (1.279-1.666)

      Histology

      Biphasic vs Sarcomatoid

      0.737 (0.675-0.805)

      Epithelioid vs Sarcomatoid

      0.460 (0.432-0.491)

      NOS vs Sarcomatoid

      0.552 (0.518-0.587)

      Sex

      Female vs Male

      0.817 (0.779-0.857)

      Year

      Unit=1

      0.984 (0.977-0.990)

      Insurance

      Medicaid vs Private

      1.193 (1.043-1.364)

      Medicare vs Private

      0.993 (0.940-1.048)

      Other/None/Unknown vs Private

      1.038 (0.938-1.148)

      Stage

      IB vs IA

      1.156 (1.088-1.228)

      II vs IA

      1.229 (1.056-1.431)

      IIIA vs IA

      1.442 (1.164-1.788)

      IIIB vs IA

      1.459 (1.379-1.544)

      IV vs IA

      1.801 (1.695-1.913)

      Treatment

      Chemo vs None

      0.613 (0.584-0.643)

      Chemo, Radiation, & Surgery vs None

      0.450 (0.396-0.512)

      Chome & Surgery vs None

      0.468 (0.436-0.504)

      Other vs None

      0.737 (0.682-0.796)

      Surgery vs None

      0.694 (0.638-0.756)

      survival_treatment.jpgmedianos_trend.jpeg

      Conclusion

      Survival outcomes in mesothelioma remain poor. There is a need for more clinical trials using combinatorial approaches to improve outcomes in mesothelioma.

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      P1.06-22 - Pathologic and Imaging Response Correlations in Patients Treated with Neoadjuvant Chemotherapy for Mesothelioma (ID 846)

      09:45 - 18:00  |  Author(s): Aaron S. Mansfield

      • Abstract

      Background

      In light of the emergence of neoadjuvant immunotherapy for the treatment of non-small cell lung cancer, there has been interest in developing neoadjuvant therapies with immune-checkpoint inhibitors for mesothelioma. Neoadjuvant trials allow the incorporation of pathologic responses as endpoints which have not been validated for mesothelioma. We sought to assess the correlation between pathologic and imaging responses in the neoadjuvant setting in patients with mesothelioma.

      Method

      We identified patients with mesothelioma who were treated with neoadjuvant chemotherapy and underwent subsequent resection at Mayo Clinic Rochester, MN from 2000-2017. We used modified Response Evaluation Criteria in Solid Tumors (RECIST) to determine radiographic responses. Imaging response was defined utilizing modified-RECIST criteria, with response defined as either complete (disappearance of all pleural and non-pleural disease) or partial (>30% decrease) response and imaging non-response was defined as either progressive (increase in size by 20% and 5 mm from nadir) or stable (meeting criteria for neither) disease. All cases were reviewed by a thoracic pathologist (ACR) to confirm the diagnosis and to define the pathologic response, which was performed blinded to the imaging response. For the purpose of this exploratory study we defined pathologic response as percent viable tumor 50% or less and non-response as >50%.

      Result

      We identified 22 patients with sufficient data and tissue available for inclusion in our study. The median age was 65 (range 48-74). There were 20 patients with epithelioid, 2 with biphasic and 0 with sarcomatoid subtypes of mesothelioma. There were 12 (55%) patients with radiographic responses and 9 (41%) with pathologic responses. Five patients had both a pathologic and imaging responses, 7 patients did not have a pathologic response but had an imaging response, 4 patients had a pathologic response without an imaging response, and 6 patients had neither a pathologic nor imaging response (χ2= 0.0063, p=0.937).

      Conclusion

      Since neoadjuvant trials have the potential to improve survival, and may be used to assess drug efficacy and accelerate drug approvals, it is important to have a unified and effective strategy to determine responsiveness of drug therapy. In our single institution, retrospective series we did not identify a significant correlation between imaging and pathologic responses which might be, at least in part, to the fact that mesotheliomas often have large areas of necrosis even without neoadjuvant therapy. Larger studies will be needed to define appropriate pathologic response endpoints in neoadjuvant trials for mesothelioma.

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    P1.12 - Small Cell Lung Cancer/NET (ID 179)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.12-11 - Exploring Sex Differences in Small Cell Lung Cancer: Is This a Hormonal Issue? (ID 605)

      09:45 - 18:00  |  Author(s): Aaron S. Mansfield

      • Abstract
      • Slides

      Background

      Small cell lung cancer (SCLC) accounts for about 10% to 15% of lung cancers among women and men. Though heavily associated with smoking, its incidence in women is rapidly increasing despite a decline in cigarette exposure. Given the changing demographics of SCLC and hormonal factors associated with other forms of lung cancer, we studied differences between sexes in SCLC.

      Method

      Utilizing the National Cancer Database, we identified all incident SCLC cases from 2004 to 2014. Patients were classified as limited (LS) or extensive stage (ES). Women were stratified by menopausal status (≥55 years = postmenopausal). Kaplan-Meier method and Cox regression were used for overall survival (OS) and multivariable analysis.

      Result

      161,978 patients were identified. No significant sociodemographic differences were observed between sexes. The majority of patients were non-Hispanic whites (89.1%), followed by non-Hispanic blacks (7.5%). Men were more likely to be diagnosed with ES disease than women (63% vs. 56%). Both sexes initiated treatment within a similar time frame from diagnosis (chemotherapy, median 18 days, IQR 8-32). Women had better median OS compared to men in both LS (15.2 vs. 12.7 months, HR: 0.85, 95% CI 0.83-0.86, p < 0.0001) and ES (6.4 vs. 5.7 months, HR: 0.88, 95% CI 0.87-0.90, p < 0.0001). No racial or ethnic disparities in OS were observed, overall and when examined within sex and disease stage groups. Differences between sexes in OS were also observed when comparing patients within the same racial/ethnic group (women having better OS). When divided by menopausal status, postmenopausal women with LS and ES had worse OS than premenopausal women (14.7 vs. 22 months, HR: 1.50, 95% CI 1.44-1.56; 6.1 vs. 9.8 months, HR: 1.41, 95% CI: 1.37-1.46, respectively). We also observed worse OS in older men when divided by age (<55 years and ≥55 years). In multivariable analysis, older age, postmenopausal status, and Medicaid as primary insurance were associated with worse OS for both LS and ES.

      Conclusion

      In this large cohort, women with SCLC had better OS compared to men. Post-menopausal women had worse OS compared to pre-menopausal women. Since older men had a similar trend of worse survival compared to younger men, age might exert a more significant influence on survival than hormonal status in SCLC. Further studies with data on sexual hormone levels are necessary to better understand their role in women with SCLC.

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    P1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 186)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.16-14 - Effects of an Artificial Intelligence (AI) System on Clinical Trial Enrollment in Lung Cancer (ID 548)

      09:45 - 18:00  |  Author(s): Aaron S. Mansfield

      • Abstract
      • Slides

      Background

      Clinical trials offer cancer patients access to the latest promising therapies and improve the overall quality and safety of cancer care. However, few patients participate, due in part to the time and effort associated with traditional manual ad hoc screening methods. IBM Watson Health’s Clinical Trials Matching (CTM) is an artificial intelligence (AI) system that employs natural language processing to abstract patient and trial data from unstructured sources and machine learning to match patients to trials. This study compared the clinical trial enrollment rates of lung cancer patients before and after deployment of CTM.

      Method

      CTM was trained for lung cancer and adopted in an academic outpatient oncology clinic using a phased implementation approach beginning July 2018. Clinical trials included ~42 therapeutic, supportive care, and observational trials. Clinical research coordinators validated Watson-derived clinical trial matches on the day prior to patient clinic visits. Oncologists were provided with a list of potentially eligible trials for each patient to facilitate evaluation at point of care. The average monthly enrollment rates for therapeutic trials were compared 6 months before and after CTM deployment. Average enrollment rates per active clinical trial were reported.

      Result

      Clinical trial matches were validated and delivered to lung oncology providers in 69% (1818/2637) of patients’ visits during the 6-month phased implementation. Enrollment of patients in lung cancer therapeutic clinical trials occurred at a rate of 3.83 patients/month after CTM deployment, as compared to 1.83 patients/month prior to CTM deployment; a 109% enrollment increase. When adjusted for the average number of active clinical trials before (30) and after (39) CTM implementation, the enrollment was 0.097 patients/trial using CTM, compared to 0.061 patients/trial using traditional methods; a 58.4% enrollment increase.

      Conclusion

      Use of IBM Watson Health’s Clinical Trials Matching (CTM) system with screening coordinators facilitated an increase in clinical trial enrollment and promoted awareness of clinical trial opportunities within the lung oncology practice.

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    P2.12 - Small Cell Lung Cancer/NET (ID 180)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.12-24 - Underutilization of Surgery for Localized Small Cell Lung Cancer: A Nationwide Analysis (ID 832)

      10:15 - 18:15  |  Author(s): Aaron S. Mansfield

      • Abstract

      Background

      Although surgery has been recommended in node-negative localized small-cell lung cancer (SCLC), utilization has been low (<10%) in the past. Here, we evaluate treatment patterns and outcomes of surgery in localized SCLC over the last decade to determine if routine practice follows the growing literature in support of surgery in localized SCLC.

      Method

      We queried years 2006-2014 of the National Cancer Database, a hospital dataset capturing 70% of incident cancers in the United States, to identify adults with Stage IA to IIA (T1-T2N0M0) SCLC who underwent treatment. Temporal practice patterns and multivariable survival outcomes were assessed.

      Result

      In the cohort of 5877 patients, 2892 (49%) received chemoradiation, 1300 (22%) received surgery with radiation or chemotherapy, 639 (11%) received chemotherapy alone, 628 (11%) received surgery alone, and 418 (7%) received radiation alone. Amongst patients receiving surgery, 1277 (66%) received a lobectomy or pneumonectomy. Likelihood of receiving surgery in combination with radiation or chemotherapy was higher in later years of diagnosis (15% in 2006 vs 25% in 2014, p<0.001). Stage IA was more prevalent in the group that received surgery alone (77%) or surgery with chemotherapy or radiation (75%) compared to chemoradiation (45%), chemotherapy (49%), and radiation (63%).

      Median overall survival was most favorable for surgery with chemotherapy or radiation (51.8 months) followed by surgery alone (33.2 months) compared to chemotherapy + radiation (26.2 months), radiation alone (17.8 months), and chemotherapy alone (11.8 months)(p<0.001). In a multivariable Cox model (Table), surgery with chemotherapy and/or radiation was associated with decreased mortality versus chemoradiation (hazard ratio=0.6, P<0.001).

      Hazard ratio

      95% CI

      Treatment

      Chemoradiation

      Chemotherapy alone

      Radiation alone

      Surgery alone

      Surgery + chemotherapy or radiation

      Ref

      2.1

      1.4

      0.9

      0.6

      1.9-2.3

      1.2-1.6

      0.7-0.9

      0.6-0.7

      Female sex

      0.8

      0.8-0.9

      Stage

      IA

      IB

      IIA

      Ref

      1.1

      1.2

      1-1.2

      1.1-1.3

      *Model also included age, insurance, median income quartile, Charlson comorbidity score, region, and race (not shown)

      sclung_surv_bytrt_figure1_040919.jpg

      Conclusion

      Utilization of surgery in localized SCLC remains low, despite its association with improved survival. Future clinical trials may be needed to establish the best therapeutic strategy for these patients.