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Marta Jimenez



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    P3.03 - Biology (Not CME Accredited Session) (ID 969)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.03-27 - Somatic BRCA1/2 Mutations in Advanced NSCLC Patients: Description of a Sub-Population from the Ongoing Unicancer SAFIR02-Lung / IFCT-1301 Trial (ID 13332)

      12:00 - 13:30  |  Author(s): Marta Jimenez

      • Abstract
      • Slides

      Background

      Molecular profiling is considered standard of care in advanced NSCLC. Identification of druggable molecular alterations may enhance the percentage of patients suitable for personalized treatment.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      From 04/2014 to 03/2017, 602 newly diagnosed,advanced NSCLC patients (pts) were enrolled in SAFIR02-Lung trial (NCT02117167). Molecular profile provided information on copy number alterations and mutations on 71 oncogenes and tumor suppressor genes. The profile was performed for 420 pts (70%) on archival tissue or frozen tissue collected from a new biopsy performed before the 3rd cycle (tissue or liquid) of chemotherapy. The frequency of BRCA mutation (mut) was assessed and clinicopathologic data collected. A homologous recombinant deficiency (HRD) score was performed on the copy number variations (CNV) data and the germline status was based on blood analysis. The BRCAshare database was the reference for the variants classification.

      4c3880bb027f159e801041b1021e88e8 Result

      18 pts were identified with BRCA alterations. BRCA variants of unknown significance were detected in 11 pts (2.6%). Response to chemotherapy according to RECIST 1.1 by investigator was: 6 stable disease (SD), 1 partial response, and 4 progressive disease (PD). CNV profile was evaluable for HRD in 6 out of 11 pts, with 50% positive.

      Seven pts (1.7%) were identified with deleterious BRCA-mut. 2 pts (0.5%) harboured germline BRCA2-mut (1 with breast cancer familiar history). Both pts had SD to chemotherapy. Somatic BRCA-mut was identified in 5 pts (1.2%, 2 BRCA1- and 3 BRCA2-mut). All were male, 100% adenocarcinoma, 75% smokers of 40 pack/year, 1 pt with familial cancer history, and 80% of pts had bone metastases. Response to chemotherapy was: 4 SD, and 1 PD. Three of 7 corresponding CNV profiles were evaluable for HRD score analysis with 100% positive.

      N=420

      BRCA alterations (N=18)

      BRCA VUS

      N=11

      BRCA deleterious

      N=7

      Somatic

      6

      5

      Germline

      5

      2

      HRD positive- Somatic

      Germline

      3/6*

      2

      1

      3/3*

      3

      0

      VUS: variants of unknown significance

      *Amongst patients with available samples for analysis
      8eea62084ca7e541d918e823422bd82e Conclusion

      Pathogenic BRCA1/2 mutations occur in 1.7% of advanced NSCLC with 71% of somatic mutations suggesting its value for exploring new therapeutic strategies in this population

      6f8b794f3246b0c1e1780bb4d4d5dc53

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