Virtual Library

 x 
My Library Virtual Library FAQ

Start Your Search

F. Cappuzzo



Author of

  • +

    MO16 - Prognostic and Predictive Biomarkers IV (ID 97)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      MO16.01 - Different Micro-RNA expression in lung adenocarcinoma with molecular driver events (ID 2316)

      16:15 - 16:20  |  Author(s): F. Cappuzzo

      • Abstract
      • Presentation
      • Slides

      Background
      Oncogenic driver alterations identify several types of lung adenocarcinoma with different prognosis and sensitivity to targeted agents. MicroRNAs (miRNAs) are a new class of non-coding RNAs involved in gene expression regulation. How miRNAs are dysregulated in lung cancer with ALK translocation, EGFR or KRAS mutation is largely unknown. In the present analysis we aimed to investigate miRNAs expression according to a specific molecular driver and to correlate miRNAs deregulation with patient outcome.

      Methods
      The study was conducted in a cohort of 67 lung adenocarcinoma patients (pts) including 17 ALK+ tumors, 11 ALK-/EGFR mutation+, 15 ALK-/KRAS mutation+, 24 ALK-/EGFR and KRAS wild-type and defined as triple negative cases. Matched normal lung tissues from 18 cases representative of the entire cohort were also included onto the analysis. RNA was isolated from formalin-fixed paraffin-embedded tissue (FFPE), using the Recover ALL kit (Ambion). NanoString nCounter system platform was used to generate the miRNA profile. We used Limma to test for differential expression analysis of data. Among the miRNAs evaluated, the miR-515 family expression between tissues was validated by RT-qPCRs, analyzed using the parametric t-test (unpaired, 2-tailed for validation).

      Results
      miRNA expression profile clusters distinctly ALK+ pts from ALK- and normal lung tissue. Within the ALK- group we found specific miRNAs subsets able to sub-stratify KRAS versus EGFR careers clustering sharply triple negative versus EGFR mutation+ and triple negative versus KRAS mutation+. miRNAs belonging to the miR-515 family seems to be the most deregulated in the ALK+ versus ALK-. Although their expression is stably high in normal tissues and ALK+ class, they are highly downregulated in KRAS mutated versus EGFR mutated and versus triple negative (p-value <0.001 for all comparisons).

      Conclusion
      miRNAs profile significantly differs in lung cancer pts with ALK translocation, EGFR mutations and KRAS mutations. Putative targets of deregulated miRNAs are under investigation to better define differences in driver-dependent pathway activation.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MO24 - NSCLC - Chemotherapy III (ID 110)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      MO24.02 - Treatment decisions for elderly patients with advanced non-small cell lung cancer (NSCLC) in Italian clinical practice: results from the RIGHT-3 project by Italian Association of Medical Oncology (ID 3115)

      10:35 - 10:40  |  Author(s): F. Cappuzzo

      • Abstract
      • Presentation
      • Slides

      Background
      In 2004, the Italian Association of Medical Oncology (AIOM) created the RIGHT (Research for the identification of the most effective and highly accepted clinical guidelines for cancer treatment) program. The third step of the program, RIGHT3, aimed to evaluate the concordance between AIOM lung cancer guidelines and clinical practice in Italy. Description of treatment decisions for elderly patients with advanced non-small-cell lung cancer (NSCLC) was among the indicators. According to 2009 AIOM guidelines, single-agent chemotherapy with a third-generation agent was a reasonable choice for elderly patients with advanced NSCLC, whilst evidence about use of platinum-based treatment in the elderly population was judged potentially affected by selection bias and not conclusive.

      Methods
      RIGHT3 was a retrospective observational study conducted in a sample of 53 Italian lung cancer centers, representative of 230 AIOM centers. Patients with NSCLC diagnosis who had their first visit at the oncology center during 2010 and followed-up for at least 6 months were included. Proportion of elderly patients with stage IV disease receiving chemotherapy was among the 14 indicators evaluated.

      Results
      Overall, 306 pts with stage IV NSLSC were enrolled, and 299 were evaluable. Of these, 91 (30.4%) were older than 70. In the elderly subgroup, 81 pts (89%) were treated with first-line chemotherapy. In detail, a single-agent treatment was administered in 28 (34.6%) of cases, and a combination chemotherapy in the other 53 cases (65.4%). Among pts receiving platinum-containing doublets, carboplatin was more frequently used than cisplatin: carbo-gemcitabine (16 pts), carbo-pemetrexed (12 pts), cisplatin-pemetrexed (8 pts), cisplatin-gemcitabine (7 pts), carbo-vinorelbine (4 pts) were the 5 most frequently used regimens.Thirty pts (33%) received a second-line chemotherapy: single-agent in 23 cases, combination chemotherapy in 7 cases.

      Conclusion
      First-line platinum-based combination chemotherapy was commonly used in elderly patients with advanced NSCLC in 2010 by the Italian Lung cancer centers involved. First-line single-agent treatment, recommended by AIOM 2009 guidelines as the treatment choice with highest level of evidence, was used only in a minority of patients.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    O03 - NSCLC - Targeted Therapies I (ID 113)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      O03.08 - DISCUSSANT (ID 3950)

      11:45 - 12:00  |  Author(s): F. Cappuzzo

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P1.11 - Poster Session 1 - NSCLC Novel Therapies (ID 208)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      P1.11-033 - Afatinib in EGFR mutant non-small-cell lung cancer patients with acquired resistance to reversible EGFR-TKIs (ID 2285)

      09:30 - 09:30  |  Author(s): F. Cappuzzo

      • Abstract

      Background
      Afatinib, an irreversible EGFR-HER2 dual inhibitor, demonstrated superiority versus standard platinum-based chemotherapy as front-line therapy in non-small-cell lung cancer patients (NSCLC) with activating Epidermal Growth Factor Receptor (EGFR) mutations. In pretreated NSCLC afatinib failed to improve survival when compared to placebo in patients refractory to gefitinib or erlotinib and not selected for EGFR status. Aim of the present study was to evaluate clinical efficacy of afatinib in EGFR mutant NSCLC patients (pts) with secondary resistance to reversible EGFR-TKIs.

      Methods
      We retrospectively analyzed a cohort of 97 EGFR mutant lung cancer pts resistant to EGFR-TKI according to criteria used in the LUX-Lung 1 trial (Miller VA, Lancet Oncol 2012) and treated with Afatinib at the daily dose of 40-50 mg. The drug was given as compassionate use.

      Results
      The study included individuals with a median age of 62,5 year. The majority were females (N=63/64.9%), never/former smokers (N=94/96,9%), with good performance status (ECOG PS 0-1; N=90/90.2%) and pretreated with > 3 therapy lines (N=68/70.0%). EGFR status was assessed in tumor tissue obtained at the time of original diagnosis. The majority of pts (N=64, 66%) harbored a deletion in exon 19, while T790M mutation was detected in two cases including one case with double exon 19 and T790M mutation. Among the 95 pts evaluable for toxicity, 54.7% had any grade skin rash, including 11.6% with grade 3, and 50,5% had any grade of diarrhea, with grade 3 recorded in 10,5%. Among the 87 pts evaluable for efficacy, response rate (RR) was 11.5%, with a median progression free-survival and overall survival of 3.9 months and 7.3 months respectively. In 25 pts a tumor biopsy was repeated immediately before starting Afatinib therapy and 1 patient out of 5 individuals harboring T790M mutation showed a short extracerebral partial response, with following brain progression.

      Conclusion
      Our findings suggest that afatinib is modestly effective in EGFR mutant NSCLC with acquired resistance to reversible EGFR-TKIs.