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Vladmir Cláudio Cordeiro De Lima



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    EP1.04 - Immuno-oncology (ID 194)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 2
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.04-44 - Exploration of Factors Relating to Paradoxical Immune Response in Patients Treated with Immune Checkpoint Inhibitors for NSCLC (Now Available) (ID 2634)

      08:00 - 18:00  |  Author(s): Vladmir Cláudio Cordeiro De Lima

      • Abstract
      • Slides

      Background

      Although the introduction of immune checkpoint inhibitors (ICIs) has yielded substantial benefits in terms of survival in the treatment of Non-Small Cell Lung Cancer (NSCLC), the possibility of activation of dormant autoimmune diseases or onset of immune mediated toxicities is a reality. The objective of this study was to explore intrinsic immunological factors associated with poor outcomes.

      Method

      In a retrospective cohort study of 48 patients, without any prior medical history of autoimmunity, treated for advanced/metastatic NSCLC with ICI´s were assessed. Determination of HLA-A*02011 as well as acute phase reactants and antiphospholipid antibodies was performed. Additionally, evaluation of survival in a time to event manner was conducted using the Kaplan Meier method and Cox regressions

      Result

      Median follow-up was 27.3 months, of the included patients 26 were male (54%) with a median age of 62 years old and there were no individuals with and ECOG performance score >1. Median overall survival (OS) was reached at 22.47 months. When analyzing the presence of the HLA-A*02011 serotype, 6 patients tested positive (12.5%). Additionally, all presented with borderline or abnormal B2glycoprotein IgM and IgG, 2Bmicroglubulin and elevated C reactive protein. Four patients (66%) experienced reactive lymphadenopathy during treatment and all suffered some form of venous thromboembolism. When analyzing OS, this group of patients had a significantly worse outcome (6.53 vs 22.47 months, HR= 4.47, [95%CI 1.47 – 13.61], p<0.001) compared with their counterparts. Overall response rate for the whole was superior for the HLA-A*02011 positive patients achieving 41.4% and 33%, p<0.001, respectively.

      Conclusion

      The presence of the HLA-A*02011 could potentially predispose to a paradoxical and pathological activation of the immune system without offering any benefit in terms of tumor control. Larger studies validating these findings are warranted.

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      EP1.04-45 - Relevance of Antibiotic Use on Clinical Activity of Immune Checkpoint Inhibitors in Hispanic Patients with Advanced NSCLC (CLICAP-ABs) (Now Available) (ID 2674)

      08:00 - 18:00  |  Author(s): Vladmir Cláudio Cordeiro De Lima

      • Abstract
      • Slides

      Background

      The composition of gut microbiota affects antitumor immune responses, as well as preclinical and clinical outcomes following immune checkpoint inhibitors (ICI) in cancer. Antibiotics (ATB) alter gut microbiota diversity and composition leading to dysbiosis, which may influence the effectiveness of ICI.

      Method

      We examined patients with advanced non-small-cell lung cancer (NSCLC) treated with anti-programmed cell death ligand-1 mAb monotherapy alone or in combination in three different countries of Latin America. Those receiving ATB within 30 days of beginning ICI were compared with those who did not. Objective response, progression free survival (PFS) and overall survival (OS) were assessed.

      Result

      18 of 140 (13%) NSCLC patients received ATB. The most commonly used ATB were b-lactam or quinolones for pneumonia or urinary tract infections. In NSCLC patients, ATB was associated with 4 cases of primary PD (28.6% versus 31.5%, P=0.818), non-significant decreased PFS (median 2.66 versus 1.94 months, HR 1.63, [95% CI 0.71-3.72], P=0.247) and significantly deleterious OS (median 12.42 versus 2.04 months, HR 2.3, [95% CI 1.08-4.95], P=0.03). In multivariate analyses, the impact of ATB remained significant for OS.

      Conclusion

      ATB were associated with reduced clinical benefit from ICI in Hispanic patients with NSCLC. Modulation of ATB-related dysbiosis and gut microbiota composition may be a strategy to improve clinical outcomes with ICI.

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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: 2
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.15-28 - Survival of Thymoma Is Extensive in Latin-American Patients: Results from Over 10 Years of Experience (CLICaP-LATimus) (ID 2936)

      08:00 - 18:00  |  Author(s): Vladmir Cláudio Cordeiro De Lima

      • Abstract

      Background

      Thymomas are a group of rare neoplasm of the anterior mediastinum. Due to their low incidence, large cooperative studies are required to evaluate outcomes. The objective of this study is to present the results and experience in treatment of this pathology in Latin-America.

      Method

      A retrospective multicenter cohort study was conducted by The Latin-American Consortium for the Investigation of Lung Cancer (CLICaP). Patients with histologically proven thymomas between 1997 and 2018 were included in the analysis. Variables including clinical, pathological and therapeutic outcomes were registered in a centralized manner.

      Result

      A total of 105 patients were included. Median age at diagnosis was 54 years old (20-84), and with 60% (n = 38) of the included patients were female. Only 11% (n=7) of the patients had an ECOG performance score >1. Twenty-four patients (22.9%, 95%CI 14.8-30.9) presented with pulmonary or distant metastatic involvement with a median of 2 metastatic sites. Furthermore, 21.9 % of patients (n=23, 95%CI 13.9-29.8%) concurrently presented myasthenia gravis. Surgery was performed in 55 patients (52.3%, 95%CI 42.8 – 61.9%), comprising of 15 tumorectomies, 37 thymectomies and 5 biopsies achieving an R0 resection rate of 78% (95%CI 67.3-89.1%). Adjuvant treatment in the form of either chemotherapy, radiotherapy or both was offered to 3(5%), 7(12.7%) and 5(9%) patients, respectively. Disease progression was documented in 10 cases (9%, 95%CI3.9-15.1%) of which 6 (60%) were locoregional, 1 (10%) distant progression and 3 (30%) both locoregional and distant. Median overall survival (OS) was estimated at around 139.5 months (95%CI 86.1-NA). Cox regression indicated that OS was significantly improved by resection (139.5 vs 25.7 months, HR 4.17 [95%CI 12.6-17.8 months]).

      Conclusion

      Survival in patients with thymomas continues to be very favorable, especially in patients who receive adequate local control. The benefit of adjuvant treatment in this setting remains unclear.

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      EP1.15-29 - Real World Characterization and Treatment of Patients with Thymic Carcinoma: Lessons from a Latin-American Study (CLICaP-LATimus) (Now Available) (ID 2921)

      08:00 - 18:00  |  Author(s): Vladmir Cláudio Cordeiro De Lima

      • Abstract
      • Slides

      Background

      Thymic carcinoma is a rare tumor that represents a clinical challenge, especially in resource limited settings. The objective of the present study was to characterize patients who presented this disease in Latin-America.

      Method

      From 2014 until 2018, a multinational Latin-American cooperative retrospective cohort study was performed. Patients with histologically confirmed thymic carcinoma were included. Clinical, pathological and treatment variables were collected across 7 participating nations.

      Result

      A total of 31 patients were included. Median age at diagnosis was 58 years old (34-69), 48% (n=15) of individuals were women with all but 2 patients (6.5%) achieving an ECOG performance score <2. All patients debuted with Stage IV disease; 24 patients (66%, [95%CI 62-92%]) as stage IVa and 7 as stage IVb (33%, [95%CI 7-37%]) with a median LDH level of 396.5 U/L (153-1529 U/L) and a median of 2 metastatic sites. 13 (41.9%, [95%CI 25-59%]) patients received preoperatory treatment consisting of chemotherapy (n=8, 42%) and chemoradiotherapy (n=5, 16%). Among these patients only 4 (12.9%) were subjected to surgery, two of which underwent a tumorectomy and 2 a thymectomy. 28 (90%, [95%CI 79.9-100%]) received palliative chemotherapy either with sunitinib (n=7, 25%) or cytotoxic agents. Median overall survival (OS) was reached at 20.2 months (95%CI 19-NA months). Patients who received preoperative treatment had a significantly prolonged OS (17.6 vs 26 months, HR 2.93 [95%CI 1.04-8.27 months], p = 0.03).

      Conclusion

      Thymic carcinoma constitutes an aggressive disease that is often diagnosed in advanced stages. These results suggest that multimodal treatment can be beneficial even in locally advanced cases. Larger clinical trial validating these conclusions are warranted.

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    EP1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 206)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.16-39 - Prospective Epidemiological Study of Metastatic Non-Small Cell Lung Cancer (NSCLC) in Latin America – LATINO Lung (LACOG 0116) (Now Available) (ID 1405)

      08:00 - 18:00  |  Author(s): Vladmir Cláudio Cordeiro De Lima

      • Abstract
      • Slides

      Background

      Non-small cell lung carcinoma (NSCLC) is the main cause of cancer-related death in Latin America. Nonetheless, there is insufficient information regarding its epidemiology, treatment and outcomes in the region. The goals of this study are to describe disease characteristics, treatment patterns and survival for advanced NSCLC in Latin America.

      Method

      LACOG 0116 LATINO Lung is a prospective cohort study aiming to include approximately 800 patients with advanced stage NSCLC (stage III/IV at diagnosis or distant relapse of early-stage disease) from 24 sites in Brazil, Argentina, Mexico, Colombia and Chile. All consecutive newly diagnosed patients seen at each site will be invited to participate. Data on socioeconomic and demographic characteristics, medical/oncologic history and clinical-pathological characteristics will be collected at baseline. Thereafter, patients will be followed every 6 months for 3 years in order to gather information regarding treatment patterns and sequencing, reasons for treatment discontinuation, response to treatment, disease progression and overall survival. Data will be collected during medical visits or telephone calls and by medical charts review. Primary endpoint is to estimate the overall survival. Descriptive analysis of treatments and outcomes are planned. Multivariable regression methods will be applied to assess possible independent prognostic or predictive factors.

      Result

      As of April 3rd, 2019, 107 patients have been included, all of them within 16 sites in Brazil. Currently, there are 2 sites from Argentina, 2 from Mexico, 3 from Colombia and 1 from Chile awaiting regulatory approval to begin enrollment. Recruitment is planned to last until December 2019, when the estimated sample size will be achieved.figure1.png

      Conclusion

      LACOG 0116 LATINO Lung is the first Latin American lung cancer prospective cohort study that will generate real-world data on NSCLC. The study may identify gaps and inequities in a diverse population of NSCLC in Latin America and consequently raise the need for improvement and individualized approach of lung cancer care in the region.

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    OA07 - Precision Medicine Involves Biology and Patients (ID 132)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
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      OA07.04 - Discussant - OA07.01, OA07.02, OA07.03 (Now Available) (ID 3758)

      11:00 - 12:30  |  Presenting Author(s): Vladmir Cláudio Cordeiro De Lima

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    P1.04 - Immuno-oncology (ID 164)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 3
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.04-76 - Predictive Factors of Early Therapeutic Failure to Immunotherapy in Patients with Metastatic NSCLC (ID 974)

      09:45 - 18:00  |  Author(s): Vladmir Cláudio Cordeiro De Lima

      • Abstract
      • Slides

      Background

      Immunotherapy helped to improve the outcomes of patients diagnosed with metastatic NSCLC. Nevertheless, survival curves show that some patients do not benefit from treatment and progress rapidly. Identifying factors capable of predicting early failure to immunotherapy is clinically useful. We determined factors associated with disease progression before nine weeks of treatment with anti-PD1.

      Method

      We retrospectively reviewed the medical records of patients with metastatic NSCLC treated in second or more line with anti-PD1 at AC Camargo Cancer Center-Brazil, from January 2006 until April 2018. Altogether, 87 patients were identified and had pre-treatment (data collected within 30 days of immunotherapy initiation) characteristics collected. Univariate analysis was performed using binomial logistic regression (disease progression occurring till 9 weeks versus after); variables with p value < 0.20 were selected for multivariate analysis. A multivariate model to predict disease progression (DP) until 9 weeks was developed using the likelihood ratio test and Akaike Information Criteria (AIC). Median follow-up was estimated using reverse Kaplan-Meier method. Median progression-free (mPFS) and overall survival (mOS) were obtained from Kaplan-Meier curves.

      Result

      Median follow-up was 18 months (95% CI 14.0-20.3), mPFS was 3.3 months (95%CI 2.1-3.7) and mOS was 15.8 months (95%CI 7.5-25.5). Univariate analysis demonstrated that the number of metastatic sites (OR=1.79; 95%CI 1.25-2.68; p=0.002), hemoglobin level (OR=0.791; 95%CI 0.55-0.88; p=0.003), monocyte count (OR=1.24; 95%CI 1.08-1.47; p=0.004), platelet count (OR=1.44; 95%CI 1.01-2.14; p=0.051), dNLR (derived neutrophil to lymphocyte ratio) (OR=1.19; 95%CI 0.95-1.54; p=0.14), ECOG (OR=2.43; 95%CI 1.00-6.048; p=0.051), T stage (OR=2.15; 95%CI 0.78-6.14; p=0.14), N stage (OR=4.26; 95%CI 1.51-14.13; p=0.010) and treatment line (OR=0.53; 95%CI 0.22-1.25; p=0.15) were significantly associated with early treatment failure. The final multivariate model demonstrated that N stage (OR=8.14; 95%CI 1.50-44.11; p=0.015), the number of metastatic sites (OR=2.10; 95%CI 1.24-3.55; p=0.005), hemoglobin level (OR=0.62; 95%CI 0.44-0.89; p=0.010), monocyte count (OR=1.44; 95%CI 1.12-1.84; p=0.004) and dNLR (OR=1.40; 95%CI 1.03-1.91; p=0.029) are independent factors associated with DP until 9 weeks of treatment.

      Conclusion

      N stage, the number of metastatic sites, hemoglobin level (g/dL), the monocyte count and the dNLR are factors independently associated with early disease progression (until 9 weeks from immunotherapy initiation). This can help to better select metastatic NSCLC patients for anti-PD1 therapy in second line.

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      P1.04-80 - Immunotherapy-Related Thrombosis: Considerations and Associated Factors in Non-Small Cell Lung Cancer (NSCLC) Patients (ID 2724)

      09:45 - 18:00  |  Author(s): Vladmir Cláudio Cordeiro De Lima

      • Abstract

      Background

      Widespread use of immune checkpoint inhibitors (ICIs) for the treatment of lung cancer has exposed a large number of patients to these medications, increasing the incidence of rare adverse reactions such as thromboses. The present study elaborates on factors related to the occurrence of these events.

      Method

      In a retrospective cohort study, a total of 48 patients, 24 who experienced thrombosis and 24 matched controls who underwent evaluation after initiation of ICIs therapy for advanced/metastatic NSCLC, were included. Clinical and pathological as well as serum inflammatory and coagulation markers were evaluated.

      Result

      Among the 48 patients, 46% (n=26) were female, median age was 62 years old and all patients had an ECOG performance score of < 2. The median overall survival reached by the cohort was 22.47 months. Among patients who developed thrombosis there were 8 cases of deep venous thrombosis (DVT) (33%), 13 pulmonary embolisms in addition to DVT (62.5%) and 1 case of brain venous sinus thrombosis (4.2%). Apart from expected thrombosis markers such as D dimer, differences in inflammatory and immune related markers between patients who experienced thrombosis and those who did not, were observed. Abnormal values were found in the thrombosis group for B2glycoprotein 1 (33% vs 0%, OR= 4.08, [95%CI 1.65 - 12.1], p= 0.005), B2glycoprotein 1 IgG (29.2% vs 0%, OR= 4.64, [95%CI 1.73 – 16.9], p= 0.007), C Reactive protein (83.3% vs 12.5%, OR= 35, [95%CI 7.9 - 213], p< 0.001), B2microglobulin (62.5% vs 8.3%, OR= 14, [95%CI 3.11-103.7], p = 0.002), Prothrombin time (41.7% vs 4.2%, OR= 2.4, [95%CI 1.64 -3.69], p =0.01) and C Coagulation protein (50% vs 16.6%, OR =1.79, [95%CI 1.53 – 2.91], p <0.001).

      Conclusion

      Abnormalities in antiphospholipid antibodies, C reactive protein, B2microglobulin and coagulation in patients who suffered thrombosis during ICI treatment suggest that this phenomenon could be the result of immune and auto-inflammatory induced intravascular dysfunction.

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      P1.04-83 - Combining Immune Gene Polymorphism and Immune Profile Predicts Brain Metastases and Death in a Brazilian Cohort of Non-Small Cell Lung Carcinoma (ID 2026)

      09:45 - 18:00  |  Author(s): Vladmir Cláudio Cordeiro De Lima

      • Abstract

      Background

      Combining immunotherapies such as anti–PD-1 and anti–CTLA-4 agents, which target complementary pathways in the cancer-immunity cycle, might result in additive or synergistic antitumor activity, and has been suggested to improve survival of patients with advanced non-small cell lung carcinomas (NSCLC). This study was conducted to investigate whether polymorphisms of immune checkpoints genes is associated with the tumor immune cell profile and with the risk of brain metastases and death of patients with advanced stage NSCLC.

      Method

      A total of 75 NSCLC patients were enrolled. The specimens included 37 (50%) adenocarcinomas (ADC), 25 (33%) squamous cell carcinomas (SqCC), and 13 (17%) large cell carcinomas (LCC). Using multiplex immunofluorescence (mIF) and image analysis, we evaluated programmed death ligand 1 (PD-L1) expression in malignant cells (MCs), CD68+ macrophages, and cells expressing the immune markers CD3, CD8, CD57, CD45RO, FOXP3, PD-1, and CD20. We used high-throughput next-generation sequencing (NGS) to evaluate single nucleotide variants (SNVs) in immune checkpoints genes CD274 (PD-L1), CTLA-4, PDCDL1LG2 (PD-L2), LAG3 and B7H4 (VTCN1) in NSCLC by TruSeq Custom Amplicon Panel (Illumina, Inc., San Diego, CA). A total of five single nucleotide polymorphisms (SNPs) were selected: rs2297136G/A (PD-L1), rs231775A/G (CTLA-4), rs7854303C/T (PD-L2), rs870849T/C (LAG3) and rs10754339G/A (B7H4). Cell phenotype data were then integrated with clinicopathologic characteristic and next-generation sequencing gene profiles.

      Result

      The patients were 47 men (median age, 78yr) and 22 women (median age, 75yr). Tobacco history was present in 22 (30%) patients. Lymph node and brain metastases were observed respectively in 28 (37%) and 8 (10%) patients, and all the patients with brain metastases also presented lymph node metastases. Twenty-three (31%) of patients received adjuvant therapy. The percentage of MCs-PD-L1+ was < 1% (40%), 1-10% (40%) and > 10% (20%). The density of immune cells/mm2 was CD3+ (330), CD3CD8+ (110), CD3-PD1+ (85), CD68+ (58), CD68-PD-L1+ (2.5), CD3CD45RO+ (260), CD3CD45FOXP3+ (260) and CD20+ (46). The frequency of genotypes was: CTLA-4 (AA=40%; AG=25%; GG=10%), CD274 (AA=32%, GA=26%, GG=17%), PDCDL1LG2 (CC=100%), LAG3 (TC=32%, CC=31%, TT=12%) and VTCN1 (AA=57%, GA=13%, GG=5%). A significant association was found between CTLA-4 and CD20+ lymphocytes (R=-0.32; p=0.02), PD-L1and VTCN1 (R=0.26; p=0.02) and PD-L1 polymorphism and MCs-PD-L1 (R=0.26; p=0.04). Different models to predict risk of death were constructed by Cox Regression analysis. Initially, the model was constructed with patient age, histologic type, N stage, brain metastases and adjuvant treatment (p<0.05). Thus CTLA-4, CD274, PDCDL1LG2, LAG3 and VTCN1 genes were included in the model (p<0.05). The second model excluded PDCDL1LG2, VTCN1 genes and introduced MCs-PD-L1 and CD3CD8+, (p<0.05). The final model, controlled for age, histologic types and adjuvant treatment, reliably predicted low risk of brain metastases and death for patients in N1 stage (β coefficient=3.24; p=0.01), CTLA-4 rs231775 AG genotype (β coefficient=-3.71; p=0.04); CD274 rs2297136 GA genotype (β coefficient= -8.55; p=0.03), LAG3 rs870849 TC genotype (β coefficient=2.16; p=0.04), low density of MCs-PD-L1 (β coefficient=6.43, p=0.04) and high density of CD3+CD8+ lymphocytes (B coefficient=-3.06; p=0.04).

      Conclusion

      Incorporating immune checkpoints genes polymorphisms into immunoprofiling score improves prediction of brain metastases and death in Brazilian NSCLC and may be promise as combining target therapy.

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    P1.09 - Pathology (ID 173)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Pathology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.09-02 - Comprehensive Genomic Profiling of Non-Small Cell Lung Cancer in Brazil (GBOT 0118/LACOG 0418) (Now Available) (ID 2048)

      09:45 - 18:00  |  Author(s): Vladmir Cláudio Cordeiro De Lima

      • Abstract
      • Slides

      Background

      Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide. Cancer driver mutations have been examined extensively and are the basis for modern precision therapy. The access of genomic tests in Brazil and, therefore, the prevalence of driver mutations of NSCLC in the country is not well described. The objective of this study is to carry out an epidemiological analysis of the somatic genetic profile of Brazilian NSCLC samples tested with FoundationOne®.

      Method

      GBOT 0118/LACOG 0418 is a retrospective cross-sectional study with patients diagnosed with NSCLC in Brazil and who performed comprehensive genomic profiling (CGP) using FoundationOne® or FoundationACT®. Raw data containing anonymous clinical-pathological characteristics and the results of CGP was analyzed. We described the molecular profile of patients using descriptive statistics. Categorical variables are presented as frequency and compared using the Chi-square test.

      Result

      We obtained a total of 513 CGP results, 457 (89.0%) from Foundation One® and 56 (10.9%) from FoundationACT®. Adenocarcinoma was the most common histological subtype (83.8%) followed by NSCLC NOS (16.1%). Median age at testing date was 64 years, and 51.27% were male. EGFR activating mutations were detected in 23.39% patients, ALK rearrangements in 5.65%, ROS1 rearrangements in 2.34%, RET alterations in 2.53%, BRAF mutations in 5.46%, KRAS mutations in 25,15% and NTRK fusions in 0,58% . Tumor mutational burden (TMB) analysis was available for 80.51% of samples tested and was measured in mutation per megabase. TMB were divided into three groups based on the Foundation Medicine reports: low (1-5 mutations/mb), intermediate (6-19 mutations/mb) and high (≥ 20 mutations/mb). The of tumors had low (42.69%) or intermediate (32.36%) TMB, and only 5.46% had high TMB.

      Table 1. Frequency of somatic genetic alterations in tumors tested with FoundationOne® and availability of targeted therapies in Brazil.

      GENE

      Frequency in NSCLC (%)

      Availability in Brazil

      EGFR

      23.39

      Approved

      ALK

      5.65

      Approved

      ROS1

      2.43

      Approved

      BRAF

      5.46

      Approved

      KRAS

      25.15

      No drugs available

      RET

      2,53

      Drugs available but not approved

      NTRK

      0,58

      Drugs available but not approved

      Conclusion

      This is the most comprehensive study describing CGP of NSCLC in Brazil using FoundationOne® or ACT. Our study shows rates of EGFR mutations and ALK rearrangements similar to those previously described. The knowledge of the molecular patterns of NSCLC in Brazil may help to improve health policies and access to targeted agents in the country.

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    P1.11 - Screening and Early Detection (ID 177)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Screening and Early Detection
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.11-38 - Frequency and Prognostic Impact of Concomitant Mutations in KRAS and TP53 or STK11 in Brazilian Lung Adenocarcinoma Patients (ID 2576)

      09:45 - 18:00  |  Presenting Author(s): Vladmir Cláudio Cordeiro De Lima

      • Abstract

      Background

      Previous studies reported that co-occurring genomic alterations in KRAS and STK11/LKB1 or TP53 tumor suppressor genes define subgroups of KRAS-mutant lung adenocarcinomas (LADC) with distinct biology, therapeutic vulnerabilities, and immune profiles. The impact of concomitant STK11, TP53 and KRAS mutations in Brazilian lung cancer patients remains poorly explored.

      Aims: In our preliminary study, we investigated the frequency of STK11 and TP53 in KRAS mutant or wild-type LADC. STK11 and TP53 mutational status was correlated with clinico-pathological characteristics and overall survival (OS).

      Method

      This is a retrospective analysis which included 27 consecutive LADC patients treated with platinum-based chemotherapy and/or immunotherapy. Mutational status analysis was performed using the Illumina TruSight Tumor 26™ panel based on multiplex-PCR. This customized multiple genes panel covers 26 critical oncogenes or tumor supressor genes including: exons 2–4 of KRAS, exons 1–9 of STK11 and 1–11 of TP53, specifically considered in the current study. Kaplan-Meier method was used to calculate overall survival and the univariate Cox model was used to compare survival.

      Result

      Among the 27 patients included, 23 (85%) were KRAS mutant (KRASmut), 15 (55.6%) were TP53 mutant (TP53mut) and 5 (18%) harbored a STK11 mutation (STK11mut). From all mutant cases, 10 (37%) were KRASmut only; 4 (14.8%) TP53mut only; 2 (7.4%) KRAS+STK11; 8 (29.6%) KRAS+TP53; 3 (11%) KRAS+TP53+STK11. No associations were observed between KRAS, TP53 and STK11 status and clinico-pathological variables. OS was shorter for TP53mut compared with wild-type patients in Cox univariate analysis (p=0.006). KRAS and STK11 status did not impact OS and progression-free survival. The co-occurrence of KRAS and TP53 mutations appears to have a detrimental effect in OS (p=0.064).

      Conclusion

      In this cohort, KRAS, TP53, and STK11 mutations were not associated with clinico-pathological features. TP53 mutations may identify a more aggressive molecular subtype of LADC.

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    P1.14 - Targeted Therapy (ID 182)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.14-61 - EGFR Inhibitors Plus Bevacizumab Are Superior Compared to EGFR Inhibitor Monotherapy in Advanced EGFR+ NSCLC Patients with BIM Deletions (ID 2697)

      09:45 - 18:00  |  Author(s): Vladmir Cláudio Cordeiro De Lima

      • Abstract

      Background

      BIM activation is essential for EGFR-TKIs triggered apoptosis in EGFR-mutant Non-small-cell lung cancer (NSCLC). A 2903-bp germline deletion in intron 2 of the BIM gene results in generation of alternatively spliced isoforms that lack the crucial BH3 domain, impairing the apoptotic response to TKIs and conferring NSCLC cells intrinsic resistance to these medications. Patients with both alterations have poor clinical evolution. The current study aimed to investigate the clinical efficacy and tolerability of EGFR-TKIs plus bevacizumab (Bev) versus EGFR-TKIs alone as first-line treatment in advanced NSCLC patients with EGFR mutations and BIM deletions (BIMdel).

      Method

      A retrospective analysis was conducted. BIMdel was detected using polymerase chain reaction (PCR) analysis and direct sequencing of DNA from tumor and peripheral blood cells (PBCs). We also assessed BIM protein expression by immunohistochemistry and BIM mRNA levels by RT-PCR. Clinical characteristics, overall survival (OS), progression-free-survival (PFS), objective response rate (ORR) and treatment-related adverse events were compared in the EGFR-TKIs versus EGFR-TKIs plus Bev groups.

      Result

      32 patients were included; 16 of them received EGFR-TKIs and 18 received EGFR-TKIs plus Bev. The addition of Bev resulted in a significantly higher ORR compared with TKIs alone (94% vs. 44%, p=0.0014). Median PFS was longer with the use of the combination compared with TKIs alone (11.1 vs. 7.77 months; p < 0.001). Median OS tended to be longer in the EGFR-TKIs plus Bev group than in TKIs alone (30.9 vs. 25.4 months; p = 0.06). EGFR-TKIs plus Bev was associated with more grade >3 hematological and thrombotic adverse events. The expression of BIM by immunohistochemistry did not influence PFS and OS, however when stratifying BIM mRNA levels by the median (≥2.2 vs. <2.1) allowed to find a prognostic trend in favor of those with higher BIM mRNA levels (32.2 vs. 25.2 months respectively; p = 0.058).

      Conclusion

      EGFR-TKIs plus Bev conferred a significantly higher ORR and PFS in advanced NSCLC patients with EGFR mutation and BIMdel. Further prospective studies are needed to validate these findings.

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    P2.11 - Screening and Early Detection (ID 178)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Screening and Early Detection
    • Presentations: 2
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.11-12 - Sputum Liquid Biopsy Provides a Non-Invasive Modality to Assess Driver Mutations and Tumor Heterogeneity in NSCLC (ID 2348)

      10:15 - 18:15  |  Presenting Author(s): Vladmir Cláudio Cordeiro De Lima

      • Abstract

      Background

      The incidence of lung cancer has significantly increased over the last century and remains the most common cause of cancer death worldwide. Our better understanding of the tumor microenvironment and of how tumors interacts with the host systemically, combined with the recent advent of the liquid biopsy, may allow non-invasive, assessment of tumor heterogeneity and evolution. Sputum has been used for the investigation of biomarkers in lung cancer since it carries airway epithelial cells, and molecular alterations identified in sputum are most likely to reflect tumor-associated changes. Our aim is to evaluate whether the molecular alterations identified in the sputum is representative of the mutations found in the tumor.

      Method

      Sputum samples were prospectively collected from 30 patients with lung adenocarcinoma at AC Camargo Cancer Center, from January 2017 till November 2018. Samples were collected at the time of diagnosis for further evaluation of actionable mutations in 14 genes, including EGFR, KRAS, BRAF and NRAS. Driver mutations were detected in 16 (53%) patients in tissue biopsy (six in KRAS and 10 in EGFR), and 2 cases also had EGFR T790M detected in circulating tumor DNA (ctDNA) isolated from plasma after disease progression post EGFR-TKI.

      Result

      Mutations were detected in 9 out of 16 sputum samples with previously known driver mutations: 3/7 with KRAS mutation (codon 12 and 61) and 6/9 with EGFR with (four exon 19 deletions, five L858R point mutations and one exon 18 G719A). Two patients with mutant KRAS detected in their sputum, did not exhibit KRAS mutations in tissue biopsy of primary tumor. One of them had a KRAS mutation detected only in a metachronous brain metastasis. EGFR T790M mutation was detected in sputum in 1 out of two samples previously positive for T790M in plasma ctDNA. All seven sputum samples negative for mutations were derived from peripheral lesions or cases with low tumor burden.

      Conclusion

      As a preliminary result, analysis of driver mutations in sputum had a good correlation with tissue biopsy (60%), especially in patients with centrally located tumors and high tumor burden, and seems to reflect tumor heterogeneity.

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      P2.11-28 - Late-Breaking Abstract - Clinical Potential of Sputum Hyaluronan Measurement in the Diagnosis and Prognosis of Patients with NSCLC (Now Available) (ID 2622)

      10:15 - 18:15  |  Presenting Author(s): Vladmir Cláudio Cordeiro De Lima

      • Abstract
      • Slides

      Background

      Lung cancer is the most frequently diagnosed and also the most lethal due to late diagnosis. Many efforts are being made to mitigate this problem. In this scenario, sputum is a potentially attractive source of biomarkers present in the extracellular matrix such as hyaluronan (HA). The aim of this study is to validate HA levels in sputum’s patients with non-small cell lung cancer (NSCLC) at the time of diagnosis and after first-line treatment evaluation response and correlate the values response rate in patients submitted to definitive treatment with chemotherapy and/or radiotherapy, progression and recurrence. We also evaluated the HA concentrations in chronic obstructive pulmonary Disease (COPD) and healthy volunteers and its impact on the screening and diagnosis of lung cancer patients.

      Method

      HA was examined in sputum samples of 64 NSCLC, 14 COPD patients and 15 healthy controls. All the patients and healthy controls selected underwent a sputum induction.The levels of HA were measured in ng/ug of protein by a noncompetitive ELISA-like fluorometric assay.

      Result

      A significant different concentration pattern of HA in the sputum was found among NSCLC (median: 33.25 ng/mg), COPD (median:16.6ng/ug) and healthy individuals (median: 12.2 ng/ug), (p<0.001, Fig. 1A), as well as NSCLC before first-line treatment (median:33.25ng/mg) and after 6 months treatment regimens with good response (median:6.2ng/ug), (p<0.001, Fig 2).

      Conclusion

      Based on the results obtained so far, we rely on the clinical potential of sputum as a screening tool in the early detection of lung cancer.

      Fig. 1A
      figure 1b.png

      Fig. 2
      figure 2.png

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