Virtual Library

 x 
My Library Virtual Library FAQ

Start Your Search

B. Han



Author of

  • +

    MO06 - NSCLC - Chemotherapy I (ID 108)

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

      MO06.13 - BEYOND: a randomized, double-blind, placebo-controlled, multicentre, phase III study of first-line carboplatin/paclitaxel (CP) plus bevacizumab (Bv) or placebo (Pl) in Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC) (ID 2756)

      17:25 - 17:30  |  Author(s): B. Han

      • Abstract
      • Slides

      Background
      Bevacizumab, a monoclonal antibody that inhibits angiogenesis via the vascular endothelial growth factor (VEGF) pathway, has proven efficacy in extending overall survival (OS) (Sandler et al, 2006) and progression-free survival (PFS) (Sandler et al, 2006; Reck et al, 2009) when added to platinum-doublet chemotherapy as first-line treatment for advanced non-squamous NSCLC. These pivotal studies included mainly Caucasian patients, however subgroup analyses in Asian patients also reported efficacy of the first-line Bv+CP regimen (Reck et al, 2009). The BEYOND study was initiated to confirm efficacy in a Chinese population.

      Methods
      Patients aged ≥18 years with histologically or cytologically confirmed, locally advanced, metastatic or recurrent advanced non-squamous NSCLC and an ECOG performance status of 0–1 were randomised 1:1 to receive CP (paclitaxel 175mg/m[2] i.v. and carboplatin AUC6 i.v. on day 1 of each 3-week cycle for up to 6 cycles), plus either Pl or Bv 15mg/kg i.v. on day 1 of each cycle, until progression, unacceptable toxicity, withdrawal of patient consent or death. Patients had no prior treatment for advanced NSCLC. Patients were stratified by gender, smoking status and age. The primary endpoint was PFS in the intent-to-treat (ITT) population; secondary endpoints included objective response rate (ORR), OS, exploratory biomarkers and safety. Collection of blood samples for biomarker analyses was mandatory (at baseline, every two cycles during treatment, at progression, and 4–6 weeks post-progression); tissue samples were optional.

      Results
      276 patients were randomised into the study, 138 to each arm. Baseline characteristics were similar in both treatment groups. PFS was prolonged with Bv+CP versus Pl+CP: hazard ratio 0.40 (95% CI 0.29–0.54); median 9.2 versus 6.5 months; p<0.0001 (ITT population). ORR was also improved with the addition of Bv to CP: 54.4% versus 26.3% with Pl+CP. Disease control rate was 94.4% versus 88.7% with Bv+CP and Pl+CP, respectively. Median duration of response was 8.0 months with Bv+CP versus 5.3 months with Pl+CP. OS data are not yet mature. Safety data were similar to previous studies of Bv+CP in NSCLC; no new safety signals were observed. Treatment discontinuation due to adverse events was 18.4% (Bv+CP) and 15.0% (Pl+CP). Treatment-related deaths were low in both arms (Bv+CP: 2.2%; Pl+CP: 0.0%). Detailed safety data and biomarker analyses will be reported.

      Conclusion
      This study confirms that the addition of bevacizumab to first-line platinum-based chemotherapy appears to provide similar PFS benefits in Chinese patients with advanced non-squamous NSCLC compared with global populations. No new safety concerns were reported.

      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.

  • +

    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

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

      P1.06-022 - Investigating the utility of plasma derived circulating free DNA for the detection of epidermal growth factor receptor (EGFR) mutations in European and Japanese patients with advanced non-small-cell lung cancer (NSCLC): ASSESS study design (ID 1801)

      09:30 - 09:30  |  Author(s): B. Han

      • Abstract

      Background
      In patients with NSCLC, accurate and accessible EGFR mutation testing is important for guiding treatment decisions. Current procedures involve the testing of biopsy or cytology samples, which are not always available from all patients. However, plasma of patients with advanced NSCLC contains circulating-free tumor-derived DNA (cfDNA) that is suitable for mutational analysis. The large, multi-center, non-interventional, non-comparative ASSESS diagnostic study (NCT01785888) will evaluate the utility of plasma-based testing compared with tissue or cytology-based testing as a less invasive methodology by which to assess EGFR mutation status in patients with NSCLC.

      Methods
      A total of 1300 patients (age ≥18 years in Europe; ≥20 years in Japan) with newly diagnosed locally advanced/metastatic (Stage IIIA/B/IV) chemotherapy-naïve NSCLC who are not eligible for curative treatment, or patients with recurrent disease after surgical resection with/without adjuvant chemotherapy, will be screened for EGFR mutation status in tumor and plasma across Japan and 7 European countries over 18 months. To allow determination of sensitivity between tumor and plasma-based EGFR screening (95% confidence interval [CI] 40-60%, assuming 50% sensitivity), 100 patients each with mutation-positive NSCLC in Europe (EGFR mutation frequency: ~10%) and Japan (EGFR mutation frequency: ~30%) will be required; 1000 and 300 patients will therefore be enrolled from Europe and Japan, respectively. Provision of tumor (biopsy/cytology/other tumor cell sample) and plasma samples for EGFR mutation testing will be mandatory. Precise clinical phenotyping will be performed, and clinical information about first line (all patients) and second line (patients with mutation-positive NSCLC) therapy decisions will be recorded. EGFR testing will be performed according to local practices, with Exon 19 deletions and L858R point mutations assessed as a minimum. The primary objective is determination of concordance between EGFR mutation status obtained via tissue/cytology and plasma-based testing (concordance rate, sensitivity, specificity, positive and negative predictive values, and exact 2-sided 95% CIs). Secondary objectives: determination of EGFR mutation frequency (including mutation subtypes) in patients with adenocarcinoma/non-adenocarcinoma NSCLC; description of first-line (all patients) and second-line (all available patients) therapy following mutation testing; characterization of current EGFR testing practices; correlation between EGFR mutation status identified in tumor/plasma samples and demographic/disease status data. Pre-planned exploratory objective: investigation of exploratory biomarkers which may help to define molecular features of NSCLC (prevalence, co-occurrence, correlation with demographic data) using optional, additional tumor (biopsy/cytology/other) samples. The secondary analyses from the study will help define the current status of EGFR mutation testing procedures across Japan and Europe, and provide further information regarding mutation frequency across patient subgroups, and the relationship between EGFR mutation status and therapy decisions.

      Results
      Not applicable.

      Conclusion
      Not applicable.

  • +

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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 2
    • +

      P1.11-021 - First-line erlotinib versus cisplatin/gemcitabine (GP) in patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC): interim analyses from the phase 3, open-label, ENSURE study (ID 1849)

      09:30 - 09:30  |  Author(s): B. Han

      • Abstract

      Background
      Erlotinib, an epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor, has proven efficacy in second-/third-line advanced NSCLC, and provides superior first-line efficacy to chemotherapy for patients whose tumors harbor activating EGFR mutations. The phase 3, randomized, open-label ENSURE study evaluated erlotinib vs GP in patients from China, Malaysia and the Philippines with EGFR mutation-positive NSCLC.

      Methods
      Patients ≥18 years with histologically or cytologically confirmed stage IIIB/IV EGFR mutation-positive NSCLC and an ECOG PS of 0–2 were randomized 1:1 to receive either erlotinib (oral; 150mg qd until progression/unacceptable toxicity) or GP (G 1250mg/m[2] iv d1 & 8 q3w; P 75mg/m[2] iv d1 q3w for up to 4 cycles). Patients were stratified by EGFR mutation type, PS, gender, and country). Primary endpoint is progression-free survival (PFS) by investigator, with Independent Review Committee (IRC) assessment for sensitivity analysis; other endpoints include objective response rate (ORR), overall survival (OS), and safety. A pre-planned interim analysis was conducted after 73% of PFS events (cut-off 20 July 2012). An additional exploratory updated analysis (cut-off of 19 November 2012), included all planned PFS events.

      Results
      In total, 217 patients were randomized: 110 to erlotinib and 107 to GP. Baseline characteristics were similar in both groups. Efficacy data by treatment arm for the interim and updated analyses are presented (Table 1). PFS by investigator in EGFR exon 19 deletion and exon 21 L858R mutation subgroups is also presented (Table 1). Erlotinib was better tolerated than GP, with treatment-related serious adverse events (SAEs) occurring in 2.7% vs 10.6% of patients, respectively. The most common grade ≥3 AEs of any cause were neutropenia (25.0%), leukopenia (14.4%) and anemia (12.5%) in the GP arm, and rash in the erlotinib arm (6.4%). At the updated analysis (19 November 2012), erlotinib remained better tolerated than GP, with treatment-related SAEs occurring in 3.6% vs 11.5% of patients, respectively. Median duration of follow-up was 10.3 months and 11.7 months for the GP and erlotinib arms, respectively, at latest cut-off. OS data are not yet mature.

      Efficacy Outcome Interim analysis (cut-off 20 July 2012) Updated analysis (cut-off 19 November 2012)
      E GP E GP
      Investigator-assessed PFS Events, n 35 66 61 87
      Median, months 11.0 5.5 11.0 5.5
      HR (95% CI) 0.34 (0.22–0.51) 0.33 (0.23–0.47)
      log-rank p-value <0.0001 <0.0001
      IRC-assessed PFS Events, n 33 47 51 55
      Median, months 11.0 5.6 11.1 5.7
      HR (95% CI) 0.42 (0.27–0.66) 0.43 (0.29–0.64)
      log-rank p-value 0.0001 <0.0001
      ORR % 62.7 33.6 68.2 39.3
      p-value 0.0001 <0.0001
      Disease control rate (DCR) % 89.1 76.6 91.8 82.2
      p-value 0.015 0.0354
      EGFR exon 19 deletion subgroup PFS Median, months 11.1 4.2 11.1 4.3
      HR (95% CI) 0.20 (0.11–0.37) 0.20 (0.12–0.33)
      EGFR exon 21 L858R subgroup PFS Median, months 8.3 7.1 8.3 5.8
      HR (95% CI) 0.57 (0.31–1.05) 0.54 (0.32–0.90)
      p-value significance level: alpha=0.05

      Conclusion
      These analyses demonstrate that erlotinib provides statistically significant and clinically meaningful improvement in both investigator-assessed and IRC-assessed PFS compared with GP in Asian patients with EGFR mutation-positive NSCLC. Primary efficacy results were also supported by secondary endpoints including ORR and DCR.

    • +

      P1.11-039 - A randomized phase II trial of celecoxib combined with platinum-based chemotherapy as first-line and with icotinib as second-line treatment for advanced non-small cell lung cancer (ID 2820)

      09:30 - 09:30  |  Author(s): B. Han

      • Abstract

      Background
      To evaluate the anti-tumor effect and safety of COX-2 inhibitors through a randomized controlled study by treating advanced non-small cell lung caner (NSCLC) with celecoxib + platinum-based chemotherapy as first-line treatment and celecoxib + icotinib as second-line treatment; to investigate the mechanism of action and efficacy predictors related to COX-2 inhibitors by detecting and monitoring serum VEGF, MMP-9 and E-cardrin in the course of treatment.

      Methods
      81 untreated patients with stage III-IV NSCLC were randomized into vinorelbine/cisplatin + celecoxib group and vinorelbine/cisplatin chemotherapy group. If disease progression was found in the followed-up visits in the middle or after the end of the 4[th] cycle, the patients would enter second-line icotinib + continued celecoxib group, while the mono-chemotherapy group became the second-line icotinib monotherapy group until the disease progressed. The patients’ serum VEGF, MMP-9 and E-cardrin were detected by ELISA assay at different time points before initial chemotherapy and after chemotherapy.

      Results
      First-line treatment and second-line celecoxib group showed significant differences in disease control rate (73.2% vs. 65.0%, P=0.036; 56.5% vs. 55.6%, p=0.078). PFS in the second-line celecoxib group was superior to that in the monotherapy group (5.3m vs. 5.0m, p=0.045). One case in the celecoxib group during second-line treatment experienced arrhythmia after continuous use of celecoxib, while the treatment was well tolerated in the other patients. After chemotherapy, serum VEGF, MMP-9 and E-cardrin were decreased, the decline in serum VEGF in the experimental group was significantly greater than that in the control group (p=0.027). Serum VEGF, MMP-9 and E-cardrin in the experimental group after chemotherapy were significantly lower than before chemotherapy (respectively: p=0.025, 0.035, 0.002). The efficacy of chemotherapy in patients with lower baseline serum VEGF and E-cardrin levels in the experimental group was better (p=0.033, 0.047). After chemotherapy, the efficacy of chemotherapy in patients with greater decline in VEGF and MMP-9 levels was better (p=0.038, 0.039). Only baseline serum VEGF was found to be related to the efficacy of chemotherapy in the control group (p=0.023). Baseline serum VEGF levels and the decline after chemotherapy were significantly associated with the patients’ PFS (p=0.019, 0.035).

      Conclusion
      COX-2 inhibitor celecoxib can improve disease control rate and be well tolerated by patients when combined with either chemotherapy for first-line treatment or targeted therapy for second-line treatment. Serum VEGF level is a good biomarker to predict efficacy and survivals, while serum MMP-9 and E-cardrin are potential biomarkers requiring large-sample studies.

  • +

    P2.12 - Poster Session 2 - NSCLC Early Stage (ID 205)

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

      P2.12-001 - Erlotinib as neoadjuvant treatment in patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) with activating Epidermal Growth Factor Receptor (EGFR) mutation (NCT01217619, EASTERN): study update (ID 260)

      09:30 - 09:30  |  Author(s): B. Han

      • Abstract

      Background
      Approximately 15% of patients with NSCLC are diagnosed with stage IIIA-N2 disease, the treatment modalities of which are not clearly defined due to its heterogeneous character. Patients with stage IIIA N2 NSCLC have poor outcomes with 5-year survival rate of approximately 15% after treatment with surgical resection or chemo-radiotherapy. Tyrosine kinase inhibitor mono-therapy as the first line treatment could significantly improve tumor response rate and disease progression free survival (PFS) for metastatic NSCLC patients with activating EGFR mutation. The objective of this trial is to explore the efficacy and safety profile of erlotinib as neoadjuvant treatment in patients of stage IIIA-N2 NSCLC with activating EGFR mutation.

      Methods
      This is a prospective, single arm, phase Ⅱ clinical trial. Patients with Endobronchial Ultrasound(EBUS) confirmed stage ⅢA-N2 NSCLC with activating EGFR mutation in exon 19 or 21 will be enrolled into the study. All the recruitment patients will be treated by erlotinib 150mg orally per day for 56 days for neoadjuvant period. Patients will be assessed after erlotinib treatment and those who get response from neoadjuvant therapy and are technically resectable will undergo surgery treatment. The adjuvant regime is decided by the investigator taking patients’ benefits into consideration. The primary endpoint is radical resection rate. The secondary endpoints are pathological complete resection rate(pCR), objective response rate(ORR), disease free survival(DFS), overall survival(OS), quality of life(QoL) and safety profile. Patients after surgery and therapy will receive long-term follow-up including regular chest CT and ultrasound examination.

      Results
      Eighty-eight(88) patients have been screened and 15 patients have been enrolled since first patients in (FPI) on 30th April, 2011. Excluded reasons including ineligible pathological diagnosis (n=23), ineligible stage (n=36), without EGFR mutation (n=10) and poor compliance (n=4). Ineligible stage including T1-3N0M0 (n=11), T1-3N1M0 (N=8), T1-3N3M0 (N=8), T1-3N2M1 (N=7) and T4N2M0 (N=2). 41% patients who were diagnosed with stage IIIA-N2 non-small cell lung cancer when in chest CT examinations were not in the stage after endobronchial ultrasound(EBUS) , and became the main reason for screening failure in this study. Seven patients had partial response, 3 patients with stable disease and 2 patients were still on treatment (DCR 66.6%). 3 patients with progress disease. Due to active hepatitis and technical infeasibility, 2 patients with partial disease didn’t receive surgery. However, one stable disease patient and five partial response patients (40%) received R0 surgery.

      Conclusion
      Neoadjuvant erlotinib therapy might be a promising treatment for IIIA-N2 NSCLC patients with EGFR activating mutation. EBUS helps the judgment of mediastinal lymph node metastasis and is better than CT scan.

  • +

    P3.05 - Poster Session 3 - Preclinical Models of Therapeutics/Imaging (ID 159)

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

      P3.05-006 - Inhibition of Tumor Cell Growth, Migration by SIM-89, a Novel Inhibitor of c-Met Tyrosine Kinase (ID 1112)

      09:30 - 09:30  |  Author(s): B. Han

      • Abstract

      Background
      It has been found that HGF-dependent c-Met（HGFR） autocrine is activated in a wide variety of human primary and second malignancies. On the other hand, the metastatic growth potential of tumors can be activated through paracrine mechanism. c-Met dysregulation leads to lung cancer development through overexpression and mutation.

      Methods
      70 kinase enzymogram screening was proceeded by Z-lyte technique. MOA analysis was completed on the inhibited kinases. Cell vitality was determined at 24h, 48h, 72h after treatment through CCK8 method. Transwell system was used to observe the inhibition of cell migration. Difference of special gene expression was evaluated by Real-time PCR. Westernblot assay was used to compare the expression difference of c-MET and p-MET. HGF level in culture medium is determined by ELISA.

      Results
      SIM-89 can inhibit 3 kinases including c-Met（IC50=297nM）, AMPK, TRKA (IC50=150.2nM). SIM-89 has an ATP competive inhibition on c-Met. By Real-time PCR, SIM-89 has been found to inhibit STAT1, JAK1, c-Met gene expression in H460 cell. P-Met expression of A549, H441, H1299 and B16F10 cell can be inhibited by SIM-89. HGF level of supernatant in culture is significantly lower than control group. Vitality of NSCLC cell lines is inhibited dependent on time and concentration by SIM-89. Induced by HGF, migration of H460, H1299 cell is inhibited.

      Conclusion
      SIM-89 has significant inhibitive effect on c-Met, TRKA kinases. It also can inhibit proliferation, migration and HGF autocrine of NSCLC cell significantly. Further study in vivo should be carried to explore the pharmacokinetics of SIM-89.