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G. Bramuglia



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    P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P2.01-060 - Biweekly Irinotecan/Bevacizumab in Heavily Treated Advanced NSCLC and Survival According to TIMP1 and EGFR Expression (ID 2521)

      09:30 - 09:30  |  Author(s): G. Bramuglia

      • Abstract
      • Slides

      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. Tissue inhibitor of metalloproteinases 1 (TIMP1) and EGFR regulates extracellular matrix catabolism and promotion of cell growth and anti-apoptotic activity in NSCLC.

      Methods:
      Forty nine patients with heavily treated metastatic NSCLC were enrolled from March 2011 to November 2014. Thirty-three (67%) had never been exposed to bevacizumab and 16 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 (treatment was repeated every 3 weeks). In all patients the mutational status of KRAS and EGFR, as well as TIMP1 and EGFR expression was evaluated.

      Results:
      The median age was 60 years (range, 44-78 years), 57% was male and 75% had ECOG 0-1. The median follow-up was 13.2 months and twenty-three patients had received >3 prior lines. The ORR was 32% (95%CI 22% to 39%) and thirteen patients (26%) achieve stable disease. Median progression-free survival (PFS) rate was 4.4 months (95%CI 2.8-8.3) and median overall survival (OS) rate was 18.0 months (95%CI 16.2-30.7). Nine patients harbouring EGFR mutations had a long-lasting, partial response (>5 months after at least 4 prior lines). Major toxicity was myelosuppression (grade 3 neutropenia occurred in 32% of patients and thrombocytopenia in 8.3%). Three patients experienced febrile neutropenia, one patient suffered grade 4 diarrhoea, and non-haematological toxicity was usually mild. Shorter OS was found in patients with a higher expression of TIMP1 mRNA (P=0.0001) but not according to the expression of EGFR (P=0.14).

      Conclusion:
      Irinotecan plus bevacizumab resulted in favourable activity and manageable toxicity profiles as third or fourth line for patients with advanced NSCLC. Our results suggested that such regimen can represent a reasonable chemotherapeutic option, especially for subjects having EGFR mutations and low expression of TIMP1.

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    P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P3.04-020 - ALK Rearrangements Epidemiology in Latin America (CLICaP) (ID 2957)

      09:30 - 09:30  |  Author(s): G. Bramuglia

      • Abstract
      • Slides

      Background:
      Latin American countries are heterogeneous in terms of lung cancer incidence, ethnicity, and exposure to potential carcinogens. The discovery of the echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) translocation as an oncogenic driver has led to the development of novel therapies with activity in vitro and in the clinic. In this study we evaluated the frequency and clinical characteristics of ALK rearrangements in six Latin-American countries.

      Methods:
      A total of 2799 biopsies of advanced NSCLC patients from 6 countries of Latin America (Argentina, Colombia, Costa Rica, Panama, Ecuador, and Mexico) were evaluated by the method fluorescence in situ hybridization (FISH) for detection of ALK-rearrangements. Demographic and clinicopathologic characteristics were analyzed.

      Results:
      The FISH analyses showed positive ALK fusion gene status in 6.55% (181/2761) of the total sample from all participating countries. ALK+ for each country was a follows: Argentina 6.08% (105/1726), Colombia 4.83% (10/207), Costa Rica 4.83% (2/49), Mexico 8.57% (64/746), and Panama 0% (0/33). Ecuador only used immunohistochemistry for ALK detection rearrangement; therefore, these samples were excluded from FISH technique analysis.

      Conclusion:
      The frequency of ALK rearrangement in Latin America is higher than previously reported for the Caucasian and Japanese populations. In addition, there is significant continental variability. Until now, FISH for ALK testing is not widely available in Latin America due to its high cost, time-consumption and result interpretation. There is an increased need to develop a common platform for genomic evaluation in developing countries.

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