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A.D. Campos Parra



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    MO10 - Molecular Pathology II (ID 127)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Pathology
    • Presentations: 1
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      MO10.02 - Update genotyping non-small cell lung cancer (NSCLC) in Latin America: Latin-American Consortium for the Investigation of Lung Cancer (CLICaP) (ID 3462)

      16:15 - 17:45  |  Author(s): A.D. Campos Parra

      • Abstract
      • Presentation
      • Slides

      Background
      Previously we reported that the frequency of mutations in EGFR and KRAS in non-small cell lung cancer (NSCLC) is Latinoamerica,finding the frequency of EGFR mutations in Latin-America between Asian (40%) and European (15%) populations. We report the update frequency of mutations in Latin America.

      Methods
      3606 biopsies of NSCLC patients from Latin-America (Argentina, Colombia, México and Peru) were used by extracted genomic DNA which was used to perform direct sequencing of EGFR gene (exons 18 and 21) and KRAS gene in 2385 samples.

      Results
      Of all patients the median age was 62.2 ±12.3, 52.6% were women, and 51% had smoking history. Frequency of EGFR mutations in NSCLC was 24.4% [CI 95% 22.7-24.1] (Argentina 14.4%, Colombia 24.9%, Mexico 34.4%, Peru 67.0%). The frequency of KRAS mutations was 7.1%. EGFR mutations were independently associated with gender (29.8% vs 16.3%; p< 0.001), older age (<60 vs >60; p= 0.001), non-smokers 25.9% vs 15.7%; p= 0.001), ethnicity (Hispanic 37.7%, Caucasic 13%, Afro-American 0%, non-determinate 22.9%; p< 0.001), histology (adenocarcinoma 23.8%, squamous 4.4%, large cells 33.3% and non differenced 22.2%) and absence of KRAS mutation. Overall response rate to tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutated patients (n=56) was 62.5% [95% CI 50-75] with a median overall survival of 16.5 months [95% CI 12.4-20.6].

      Conclusion
      Our findings confirm the high frequency of EGFR Mutation in Latino-america and low frequency of K-RAS mutation, particularly in patients of Hispanic ethnicity. Differences in risk factors associated with lung cancer in our population and ethnic variability could explain these findings.

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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 2
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      P1.06-019 - Common and uncommon EGFR mutations and their impact on response to EGFR tyrosine-kinase inhibitors and platinum-based chemotherapy in non-small cell lung cancer (NSCLC): Latin-American Consortium for the Investigation of Lung Cancer (CLICaP) (ID 1728)

      09:30 - 16:30  |  Author(s): A.D. Campos Parra

      • Abstract

      Background
      An association has been well-established between common EGFR mutations and response to reversible and irreversible direct EGFR tyrosine-kinase inhibitors (EGFR-TKIs); however, there is a significant lack of information about the impact of uncommon mutations on outcomes such as overall response (OR), progression-free survival (PFS) and overall survival (OS) rates after being exposed to EGFR-TKIs or platinum-based chemotherapy (CT).

      Methods
      Information regarding 186 NSCLC patients from three Latin-American countries was analysed. Tests were made for EGFR and KRAS mutations; the clinical and pathological characteristics and the presence of common and uncommon EGFR mutations were considered according to OR, PFS and OS rates concerning EGFR-TKIs and CT.

      Results
      79.5% of the patients had common EGFR mutations and 20.5% uncommon mutations, including complex alterations. Lepidic and acinar histological subtypes were associated with higher common EGFR mutation frequency (p= 0.010). Patients having an OR to EGFR-TKIs treatment also had an OR to CT (p< 0.001). Patients harbouring common EGFR mutations had greater sensitivity to EGFR-TKIs than those having uncommon mutations (63.8% [IC 95% 51.1-76.5] vs 32.4% [20.0-44.7] p< 0.0001). Median PFS regarding EGFR-TKIs (16.4 [12-21.1] vs 4.1 months [1.9-5.9]) and CT (16 [10.9-21] vs 4.3 months [0.9-12.9]) was better in patients having common EGFR mutations compared to patients carrying uncommon mutations. The median OS of patients treated with EGFR-TKIs that harbored common EGFR mutations (37.3 months [33.2-41]) was longer compared to those patients who harbored uncommon mutations (17.4 months [12.9-21.8]).

      Conclusion
      Our findings suggest that patients with EGFR uncommon mutations, could receive platinum-based chemotherapy as first line of treatment and EGFR-TKIs can be reserved as second or third line treatment options.

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      P1.06-042 - Klotho expression in patients having EGFR mutations (CLICaP study) (ID 2666)

      09:30 - 16:30  |  Author(s): A.D. Campos Parra

      • Abstract

      Background
      Klotho is a type I transmembrane protein which is encoded by the KL gene; it is associated with many metabolic processes in differing neoplasias, including lung adenocarcinoma. Its abnormal expression conditions irregular endothelial growth and hyperactivation of proliferation via the PI3K/Akt signalling pathway.

      Methods
      Information concerning 84 patients with epidermal growth factor receptor (EGFR) mutations was taken to explore Klotho’s cytoplasmic positivity using an anti-Klotho antibody (Calbiochem, BD Biosciences, San Jose, CA, USA; 1:100 dilution). The results were correlated with multiple outcomes, including differing clinical characteristics, response rate, progression-free survival (PFS) and overall survival (OS).

      Results
      Mean age was 60.7 years (SD±13.1) and Klotho expression in the population of patients having EGFR mutations was considered positive in 35.7% of them (n=30), negative in 31.0% (n=26) and unknown in the remaining 33.3% (n=28). Positive Klotho expression was not influenced by gender (p=0.51), histological pattern (p=0.063), base functional state (p=0.49) or a history of smoking (p=0.19); nevertheless, Klotho overexpression was greater amongst exon 19 deletion carriers (p=0.030) and in patients having the L858R mutation (p=0.009) compared to the group of subjects having infrequent mutations. EGFR mutation patients’ overall response was greater in those having increased Klotho expression compared to the population of subjects lacking reactivity or in those where evolution following the administration of any type of reversible tyrosine-kinase inhibitor remained unknown (p=0.011). Overall population PFS was 16.7 months (12-21 95%CI) after directed therapy was started; PFS lasted longer in the Klotho positive group (positive expression 21.1 months vs. negative 13.7 months; p=0.032). Median OS was 28.5 months (25.8-31.2 95%CI), longer for patients having increased Klotho expression (31.9 versus 22.0 months; p=0.039).

      Conclusion
      Klotho expression revealed by immunohistochemistry in lung adenocarcinoma patients having EGFR mutations facilitated stratifying prognosis.

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    P2.10 - Poster Session 2 - Chemotherapy (ID 207)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.10-043 - Phase II study of biweekly irinotecan plus bevacizumab in heavily treated advanced non-small cell lung cancer (NSCLC) (ID 2605)

      09:30 - 16:30  |  Author(s): A.D. Campos Parra

      • Abstract

      Background
      Irinotecan and bevacizumab are effective against non-small cell lung cancer (NSCLC) and synergism with non-cross-resistance has been demonstrated in preclinical studies.

      Methods
      Twenty-four patients having heavily treated metastatic NSCLC were enrolled from March 2011 to November 2012. Sixteen of these subjects had never been exposed to bevacizumab and 8 had received antiangiogenic therapy as part of their first-line (all had achieved a previous response for more than 6 months). Treatment consisted of a 90-min intravenous infusion of 125 mg/m[2] irinotecan on day 1 and 8 plus 7.5 mg/kg bevacizumab on day 1. The treatment was repeated every 3 weeks and all patients underwent genotype evaluation (including EGFR and KRAS mutation screening).

      Results
      One patient (4.2%) achieved a complete response and six (25%) had a partial response. Objective response rate (ORR) was 29.2% (4.6 months median response duration). Seven patients had stable disease, and disease control rate (DCR) was 58.3%. After a median follow-up of 12.8 months, median progression-free survival (PFS) rate was 4.8 months (95%CI 1.8-9.2) and median overall survival (OS) rate was 19.8 months (95%CI 9.2-30.2). Major toxicity was myelosuppression (grade 3-4 neutropenia occurred in 43% of patients and thrombocytopenia in 8.3%). Two patients experienced febrile neutropenia and non-haematological toxicity was usually mild. One patient suffered grade 4 diarrhoea, and four patients harbouring EGFR mutations had a long-lasting, partial response (>7 months after at least 4 prior lines).

      Conclusion
      The irinotecan pus bevacizumab combination resulted in favourable activity and manageable toxicity profiles as third or fourth line for patients suffering advanced NSCLC. Our results suggested that such regimen can represent a reasonable chemotherapeutic option, especially for subjects having EGFR mutations. This hypothesis can be partly supported because of topo I activity resulting from increased topo I mRNA and protein expression caused by MET signalling.

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    P2.18 - Poster Session 2 - Pathology (ID 176)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
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      P2.18-023 - Relevance of the novel IASLC/ATS/ERS classification of lung adenocarcinoma in advanced-disease non-small cell lung cancer. (ID 1741)

      09:30 - 16:30  |  Author(s): A.D. Campos Parra

      • Abstract

      Background
      Since IASLC/ATS/ERS reported their new classification for lung adenocarcinoma (ADC), several groups have validated its association with prognosis in early stage. We know do not any study in advanced disease.

      Methods
      We included 313 patients with stage IIIB and IV histologically confirmed lung ADC from the Instituto Nacional de Cancerología (INCan). All patients received platinum-based chemotherapy (CT) and only 30% received EGFR-TKIs. ADCs were re-classified using the new IASLC/ATS/ERS criteria. Clinical characteristics, mutational profile, response and progression-free survival (PFS) to CT and overall survival (OS) were analyzed.

      Results
      ADCs were classified as lepidic 6.1%, acinar 36.7%, papillary 8.3%, micropapillary 2.9%, solid 28.1% and 17.9% were unclassifiable. We divided them into two groups: intermediate-grade (lepidic and acinar-predominant) and high-grade (micropapillary, papillar and solid-predominant). The response rate and PFS to CT were better in the high grade group (36.9% vs 25.4% p= 0.034; 6.4 vs 5.5 months p= 0.009, respectively). The OS was better in the high grade group (25 vs 16.8 p= 0.023). In multivariate analysis, factors associated with better OS were ECOG of 0-1, EGFR mutations and high grade group histology. We did not find association between EGFR mutations and this classification.

      Conclusion
      Unlike early stages, patients with advance disease and with high-grade ADC according to the new classification have longer OS compared with intermediate grade ADC, probably due to a better response to CT.