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J. Mazieres



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    MO18 - NSCLC - Targeted Therapies IV (ID 116)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO18.10 - Oral MEK1/MEK2 inhibitor trametinib (GSK1120212) in combination with pemetrexed in a phase 1/1B trial involving <em>KRAS</em>-mutant and wild-type (WT) advanced non-small cell lung cancer (NSCLC): efficacy and biomarker results (ID 2922)

      16:15 - 17:45  |  Author(s): J. Mazieres

      • Abstract
      • Presentation
      • Slides

      Background
      KRAS is the most frequently mutated oncogene in NSCLC and represents an unmet need for targeted therapy. Trametinib plus pemetrexed enhances growth inhibition and apoptosis of NSCLC cell lines with and without RAS/RAF mutations in vitro when compared with either agent alone.

      Methods
      This 2-part, multi-arm, open-label phase 1/1B study evaluated the safety and efficacy of trametinib plus chemotherapy (NCT01192165). Part 1 determined the recommended phase 2 dose (RP2D) for trametinib (1.5 mg daily) and pemetrexed (500 mg/m[2] every 3 weeks) in patients with advanced solid tumors. In part 2, patients with NSCLC were stratified as KRAS WT or KRAS-mutant and treated at the RP2D. Primary study objectives were safety and tolerability; secondary objectives were efficacy and pharmacokinetics (PK). Next-generation sequencing was used to perform exploratory mutational profiling on available archival tissue from 21 patients (50%). Plasma from 38 patients (90%) was analyzed both for tumor-derived mutations in cell-free DNA (eg, KRAS, EGFR) using BEAMing technology as well as cytokine and angiogenic factors using a Searchlight multiplex assay.

      Results
      A total of 42 patients with NSCLC (19 KRAS WT [79% ≥ 2 prior therapies; 74% prior pemetrexed; 16% squamous] and 23 KRAS-mutant [57% ≥ 2 prior therapies; 43% prior pemetrexed; 4% squamous]) were enrolled and treated at the RP2D until disease progression or unacceptable toxicity. Safety and PK data were previously reported (ASCO 2013). Response rate was 17% and disease control rate was 69% for the whole population of NSCLC. Of note, we observed disease control in 75% of patients previously treated with pemetrexed (including 4 partial responses [PRs]) and in 2 patients out of 4 with squamous histology (including one PR). Progression-free survival (PFS) was 5.1 months for all patients with NSCLC. Detailed efficacy results according to mutation status are shown in Table 1. Among KRAS WT, activity was seen in cancers with EGFR mutations or ALK rearrangement. Final biomarker analyses, including assessment of their potential correlation with therapeutic response or resistance, are ongoing and will be reported upon completion. Figure 1

      Conclusion
      MEK inhibition with trametinib + pemetrexed demonstrated activity in both KRAS-mutant and WT NSCLC; efficacy data are encouraging and warrant further study. There was no significant difference in activity or efficacy across KRAS mutation subtypes. Interestingly, activity with this combination was broad and was seen in patients with squamous histology, patients with prior pemetrexed treatment, and those with EGFR mutation or ALK translocation.

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    P3.24 - Poster Session 3 - Supportive Care (ID 160)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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      P3.24-038 - Perception of lung cancer among the general population and comparison with other cancers. (ID 2692)

      09:30 - 16:30  |  Author(s): J. Mazieres

      • Abstract

      Background
      After decades of very slow progresses, lung cancer management rapidly evolved in the past few years. One could anticipate a possible leap in perception of the disease between patients and physicians.

      Methods
      We conducted a prospective nationwide observational survey of 2200 healthy subjects selected within a representative permanent polling database according to the relevant national and European laws. We collected data in relation to aetiology, epidemiology, diagnostic, therapy and prognostic by using a specific questionnaire as well as perception of lung cancer by using a lexical approach. Among them, 1629 returned the questionnaire and 1469 were eligible for a full analysis.

      Results
      We observed that the population has an average high level of information regarding epidemiological changes of lung cancer (“same incidence” for 40%, “higher incidence” for 47%, “increase in women” for 75%), and main risk factors (tobacco 93%, occupational 81% and environmental exposure 56%). Two thirds (67%) are aware of the danger of passive smoking. Only 22% of the whole population believed to be at risk of lung cancer. Differences were seen according to smoking habits as 62% of current smokers, 21% of former smokers and 6% of never-smokers believed to be at risk (p < 0.05) and according to the age, as 15% of responders above 65 years old thought to be at risk in comparison of 26% of responders below 34 (p < 0.05). The population overestimated the overall survival of lung cancer (32%) and underestimated the potential cure of early stage disease (52%). The participants clearly identified lung cancer as a severe disease (82%) with a worse prognostic than other cancers (colorectal, breast, prostate, p < 0.05). Most of the population was aware of the main treatments of lung cancer (surgery, chemotherapy and radiotherapy) but only 45% cited targeted therapy. By using lexical tests we observed that corpus can be split in two main lexical repertoires: a) the major repertoire in which the significant units have encoded lung cancer identified as a tobacco-induced, life-threatening disease, imposing heavy treatment and b) the minor repertoire in which significant units belonged to the representation of lung cancer as an environmental-induced disease. In comparison with breast cancer, lung cancer is characterized by a greater feeling of guilt and a more frequent association with the way of life.

      Conclusion
      We deciphered some aspects of lung cancer perception in the general population and anticipated that it may improve psychological adjustment in patient-doctor communication, fill in the knowledge gap of the perception of the disease and eventually help in lung cancer management.