Virtual Library

 x 
My Library Virtual Library FAQ

Start Your Search

J. Wei



Author of

  • +

    P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

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

      P2.06-012 - Impact of EGFR T790M mutations and BIM mRNA expression on progression-free survival (PFS) and overall survival (OS) in patients with EGFR-mutant non-small-cell lung cancer (NSCLC) treated with erlotinib or chemotherapy in the randomized phase III EURTAC trial (ID 1167)

      09:30 - 09:30  |  Author(s): J. Wei

      • Abstract

      Background
      Activating EGFR mutations confer sensitivity to EGFR tyrosine kinase inhibitors (TKIs) in patients with NSCLC, but responses are transient, with delay in disease progression but no impact on survival. Concomitant genetic alterations could account for these incomplete clinical responses. Erlotinib-treated EGFR-mutant NSCLC patients harboring the EGFR T790M mutation had shorter PFS than those without the mutation (12 vs 18 months [m]). Low BIM levels were associated with gefitinib resistance in EGFR-mutant NSCLC.

      Methods
      The efficacy results of the EURTAC trial were updated at January 24, 2013. We have evaluated the frequency and potential impact of pretreatment EGFR T790M mutations and BIM mRNA expression in 95 patients with EGFR-mutant NSCLC included in the EURTAC trial.

      Results
      T790M mutations were detected in 65.26% of patients. PFS to erlotinib was 9.7 m for those with T790M mutations and 15.8 m for those without, while among patients receiving chemotherapy, it was 6 and 5.1 m, respectively (P<0.0001). BIM expression was successfully analyzed in 83 patients. PFS to erlotinib was 12.9 m for those with high BIM levels and 7.2 m for those with low/intermediate BIM levels, while among chemotherapy-treated patients, it was 5.8 and 5.5 m, respectively (P=0.0003). OS was 28.6 m for patients with high BIM expression and 22.1 m for those with low/intermediate BIM expression (P=0.0364). The multivariate analyses showed that erlotinib was a marker of longer PFS (HR, 0.35; P=0.0003), while high BIM expression was a marker of longer PFS (HR, 0.49; P=0.0122) and OS (HR, 0.53; P=0.0323).

      Conclusion
      BIM mRNA expression is a biomarker of PFS and OS in EGFR-mutant NSCLC. T790M mutations and BIM mRNA expression can potentially be used for designing combination therapeutic strategies for use in lieu of EGFR TKI monotherapy.

  • +

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

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

      P2.10-031 - Chinese randomized phase II trial of customized chemotherapy based on BRCA1-RAP80 mRNA expression in advanced non-small-cell lung cancer (NSCLC) patients (p) (ChiCTR-TRC-12001860/BREC-CHINA) (ID 1883)

      09:30 - 09:30  |  Author(s): J. Wei

      • Abstract

      Background
      BRCA1 serves as a differential modulator of chemosensitivity to docetaxel (doc) and cisplatin (cis). RAP80 targets the BRCA1-BARD1 E3 ligase at double-strand breaks. A Spanish Lung Cancer Group (SLCG) phase II customized chemotherapy trial (NCT00883480) indicated that RAP80 and BRCA1 jointly influenced outcome in NSCLC p treated with cis- or doc-based chemotherapy. Based on these findings, the SLCG initiated a randomized phase III trial (NCT00617656/GECP-BREC), and we have performed a parallel phase II trial comparing non-customized cis/doc with customized therapy in metastatic NSCLC p in China.

      Methods
      Since October 2010, 104 p have been randomized 1:3 to control and three experimental arms. p in the control arm receive cis/doc; p in the experimental arm receive treatment according to their BRCA1 and RAP80 levels: p with low RAP80, regardless of BRCA1 levels, cis/gemcitabine (gem); p with intermediate/high RAP80 and low/intermediate BRCA1, cis/doc; p with intermediate/high RAP80 and high BRCA1, doc alone. The primary endpoint is progression-free survival (PFS).

      Results
      PFS was 4.15 months (m) in the control and 3.59 m in the experimental arm (P=0.68). Overall survival (OS) was 10.82 m in the control and 11.74 m in the experimental arm (P=0.68). Response rate (RR) was 23.3% in the control and 32.4% in the experimental arm (P=0.48). In ancillary analyses of p with low, intermediate and high BRCA1 levels, PFS in the control arm was 2.66, 4.15 m and 7.5 m, respectively, while PFS in the experimental arm was 10.66 m, 3.45 m and 3.06 m, respectively. In the multivariate analysis including PS, treatment arm, BRCA1, RAP80, histology and smoking status, only ex-smokers were associated with an increased risk of progression (HR, 1.906; P=0.029).

      Conclusion
      Customized chemotherapy based on BRCA1/RAP80 expression does not improve PFS. The predictive value of BRCA1 alone seems to be stronger than that of BRCA1/RAP80 combined.