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Bo Zhang



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    JCSE01 - Perspectives for Lung Cancer Early Detection (ID 779)

    • Event: WCLC 2018
    • Type: Joint IASLC/CSCO/CAALC Session
    • Track: Screening and Early Detection
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/23/2018, 07:30 - 11:15, Room 202 BD
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      JCSE01.19 - ALTER-0303 Study: Tumor Mutation Index (TMI) For Clinical Response to Anlotinib in Advanced NSCLC Patients at 3rd Line (ID 14708)

      11:15 - 11:15  |  Author(s): Bo Zhang

      • Abstract
      • Slides

      Background

      Anlotinib is an effective multi-targeted receptor tyrosin kinase inhibitor (TKI) for refractory advanced Non-Small Cell Lung Cancer (NSCLC) therapy at 3rd line. ALTER-0303 clinical trial has been revealed that Anlotinib significantly prolongs progression free survival (PFS; Anlotinib: 5.37 months vs Placebo: 1.40 months) and overall survival (OS; Anlotinib: 9.63 months vs Placebo: 6.30 months) with the objective response rate (ORR) of 9.18% and the disease control rate (DCR) of 80.95%. Here, we sought to understand the gene mutation determinants for clinical response to Anlotinib via next generation sequencing (NGS) upon cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) at baseline.

      Totally 437 advanced NSCLC patients enrolled in ALTER-0303 study, and 294 patients received Anlotinib therapy. Of the 294 patients, 80 patients were analyzed in the present study. Capture-based targeted ultradeep sequencing was performed to obtain germline and somatic mutations in cfDNA and ctDNA. Response analyses upon discovery cohort (n = 62) and validation cohort (n = 80) were performed by use of germline and somatic (G+S) mutation burden, somatic mutation burden, nonsynonymous mutation burden, and unfavorable mutation score (UMS), respectively. Based on the above independent biomarkers and their subtype factors, tumor mutation index (TMI) was developed, and then used for response analysis.

      Our data indicated that the patients harbouring less mutations are better response to Anlotinib therapy (G+S muatation burden, cutoff = 4000, Median PFS: 210 days vs 127 days, p = 0.0056; somatic mutation burden, cutoff = 800, Median PFS: 210 days vs 130 days; p = 0.0052; nonsynonymous mutation burden, cutoff = 50, Median PFS: 209 days vs 130 days; p = 0.0155; UMS, cutoff = 1, Median PFS: 210 days vs 131 days; p = 0.0016). TMI is an effective biomarker for Anlotinib responsive stratification (Median PFS: 210 days vs 126 days; p= 0.0008; AUC = 0.76, 95% CI: 0.62 to 0.89) upon discovery cohort and validation cohort (Median PFS: 210 days vs 127 days; p = 0.0006). Lastly, integrative analysis of TMI and IDH1 mutation suggested a more promising result for Anlotinib responsive stratification upon validation cohort (Median PFS: 244 days vs 87 days; p < 0.0001; AUC = 0.90, 95% CI: 0.82 to 0.97).This study provide a biomarker of TMI to stratify Anlotinib underlying responders, that may improve clinical outcome for Anlotinib therapy on refractory advanced NSCLC patients at 3rd line. Clinical trial information: NCT02388919.

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      JCSE01.21 - Different Responses to Osimertinib in Primary and Acquired EGFR T790M-Mutant NSCLC Patients (ID 14711)

      11:15 - 11:15  |  Author(s): Bo Zhang

      • Abstract
      • Slides

      Background
      Primary EGFR T790M could be occasionally identified by routine molecular testing in tyrosine kinase inhibitor TKI-naive non-small cell lung cancer (NSCLC) patients. This study was aimed to compare clinical characteristics of primary and acquired T790M mutations and their responses to Osimertinib in NSCLC patients.
      We collected clinical characteristics of patients diagnosed with epidermal growth factor receptor (EGFR) mutation from 2012 to 2017 in Shanghai Chest Hospital. For patients with primary and acquired T790M mutations, the responses to Osimertinib were analyzed.Primary T790M was identified in 1.03% (61/5900) of TKI-naive patients. Acquired T790M was detected in 45.50% (96/211) of TKI-treated patients. T790M always coexisted with sensitizing EGFR mutations. Primary T790M was always coexisted with 21L858R (45/61) whereas acquired T790M was coexisted with 19del (61/96). Among them, 18 patients with primary T790M mutation acquired Osimertinib and 75 patients with acquired T790M mutation received Osimertinib. The median progression-free survival (mPFS) of Osimertinib in primary T790M group was greatly longer than that in acquired T790M group (18.0 months:95% CI:15.0-21.0 VS 10.0months:95% CI:8.3-11.7, P=0.016). The DCR of both groups were 89.3% and 100%. In primary T790M group, the mPFS of concomitant occurrence of 20 T790M and 21 L858R or 19del were 15.7m and 24.0 m, respectively. In acquired T790M group, the mPFS of concomitant occurrence of 20 T790M and 21 L858R or 19del were 11.0m and 10.0m, respectively.

      Primary and acquired T790M-mutation patients showed different molecular characteristics. Both of them may respond to Osimertinib. However, primary T790M patients showed greater survival benefits from Osimertinib than acquired T790M patients.

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    MA01 - Early Stage Lung Cancer: Questions and Controversies (ID 894)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 202 BD
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      MA01.01 - Proposal on Incorporating Lymphovascular Invasion as a T-Descriptor for Stage I Non-Small Cell Lung Cancer (Now Available) (ID 12754)

      10:30 - 10:35  |  Author(s): Bo Zhang

      • Abstract
      • Presentation
      • Slides

      Background

      Lymphovascular invasion (LVI) and Visceral Pleural Invasion(VPI) have been reported to be risk factors for stage I Non-Small Cell Lung Cancer (NSCLC). However, only VPI was incorporated into the current 8th Tumor–Node–Metastasis(TNM) classification. This study aimed at exploring the prognostic impact of LVI on TNM staging in Pathological Stage I NSCLC.

      Method

      We retrospectively reviewed 2600 consecutive p-stage I NSCLC patients in the Shanghai Chest Hospital (2008-2012). By using the Kaplan–Meier method and Cox proportional hazard regression model, we identified the correlations between LVI, VPI and clinical outcomes in p-stage I NSCLC.

      Result

      Of all p-stage I NSCLC 2600 patients, 221 were pathologically diagnosed with LVI and 815 pathologically with VPI, respectively. It was observed that patients with LVI had an unfavorable lung cancer specific survival (LCSS) (hazard ratio [HR]: 1.883; 95% confidence interval [CI]: 1.351-2.625; P < 0.001) and recurrence-free survival (RFS) (HR: 2.025; 95% CI: 1.560-2.630; P < 0.001). The 5-year RFS rates of patients with LVI was significantly worse than those without LVI (61.2% VS 82.7%, P< 0.001). Patients with LVI exhibit similar prognosis (HR: 2.538; 95% CI: 1.570-4.098; P < 0.001) compared with that of VPI in pN0 non-small-cell lung cancer and a tumor diameter of 3cm or smaller. When tumor size was between 3-4cm, patients with LVI and VPI were associated with inferior prognosis than those with only LVI or VPI (P < 0.001).

      Conclusion

      The presence of LVI independently and significantly affects LCSS and RFS in patients with stage I NSCLC. Our results suggest that stage T1a-1c(IA) patients with LVI should be upstaged to T2a(IB), meanwhile, stage T2a(IB) patients coexist with LVI and VPI should be upstaged again in the TNM classification.

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    MA15 - Colliding Approaches - EGFR and Immunotherapy (ID 916)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/25/2018, 13:30 - 15:00, Room 107
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      MA15.07 - Different Responses to Osimertinib in Primary and Acquired EGFR T790M-Mutant NSCLC Patients (Now Available) (ID 12766)

      14:10 - 14:15  |  Author(s): Bo Zhang

      • Abstract
      • Presentation
      • Slides

      Background

      Primary EGFR T790M could be occasionally identified by routine molecular testing in tyrosine kinase inhibitor TKI-naive non-small cell lung cancer (NSCLC) patients. This study was aimed to compare clinical characteristics of primary and acquired T790M mutations and their responses to Osimertinib in NSCLC patients.

      Method

      We collected clinical characteristics of patients diagnosed with epidermal growth factor receptor (EGFR) mutation from 2012 to 2017 in Shanghai Chest Hospital. For patients with primary and acquired T790M mutations, the responses to Osimertinib were analyzed.

      Result

      Primary T790M was identified in 1.03% (61/5900) of TKI-naive patients. Acquired T790M was detected in 45.50% (96/211) of TKI-treated patients. T790M always coexisted with sensitizing EGFR mutations. Primary T790M was always coexisted with 21L858R (45/61) whereas acquired T790M was coexisted with 19del (61/96). Among them, 18 patients with primary T790M mutation acquired Osimertinib and 75 patients with acquired T790M mutation received Osimertinib. The median progression-free survival (mPFS) of Osimertinib in primary T790M group was greatly longer than that in acquired T790M group (18.0 months:95% CI:15.0-21.0 VS 10.0months:95% CI:8.3-11.7, P=0.016). The DCR of both groups were 89.3% and 100%. In primary T790M group, the mPFS of concomitant occurrence of 20 T790M and 21 L858R or 19del were 15.7m and 24.0 m, respectively. In acquired T790M group, the mPFS of concomitant occurrence of 20 T790M and 21 L858R or 19del were 11.0m and 10.0m, respectively.

      Conclusion

      Primary and acquired T790M-mutation patients showed different molecular characteristics. Both of them may respond to Osimertinib. However, primary T790M patients showed greater survival benefits from Osimertinib than acquired T790M patients.

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    OA07 - Oligometastasis: What Should Be the State-Of-The-Art? (ID 905)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Oligometastatic NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/24/2018, 15:15 - 16:45, Room 107
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      OA07.06 - Efficacy of Local Consolidative Therapy for Oligometastatic Lung Adenocarcinoma Patients Harboring EGFR Mutations. (Now Available) (ID 12523)

      16:10 - 16:20  |  Author(s): Bo Zhang

      • Abstract
      • Presentation
      • Slides

      Background

      For oligometastatic lung adenocarcinoma patients with sensitive EGFR mutations, the role of local consolidative therapy (LCT) remains debatable. The purpose of this study was to investigate the efficacy of LCT in these patients.

      Method

      Advanced stage patients with oligometastatic lung adenocarcinoma who harboring EGFR mutation were identified at the Shanghai Chest Hospital from 2010 to 2016.

      Result

      A total of 253 patients (149 patients who received LCT plus EGFR-TKIs [combination group] and 104 patients who received EGFR-TKIs [TKI monotherapy group] were included. The median PFS time in the combination group was 14 months versus 9 months in the TKI monotherapy group (HR=0.57, 95% [CI] 0.44, 0.79, p<0.01, Figure 1 A). The median OS time in the combination group was 33 months versus 20 months in the TKI monotherapy group (HR=0.56, 95% [CI] 0.41, 0.75, p<0.01, Figure 1D). Survival benefit was independent of EGFR mutation type (PFS: 19del, p=0.02, Figure 1B; 21L858R, p<0.01, Figure 1C; OS: 19del, p=0.0189, Figure 1E; 21L858R, p<0.01, Figure 1F) and metastatic sites .figure 1.jpg

      Conclusion

      LCT combined with TKI therapy was feasible and significantly improved PFS and OS among oligometastatic lung adenocarcinoma patients with sensitive EGFR mutations, and thus, should be considered as an important medical treatment during clinical management.

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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-29 - Crizotinib in Advanced Lung Adenocarcinoma Patients with ALK or ROS-1 Rearrangement: Is it the Same? (ID 12929)

      16:45 - 18:00  |  Author(s): Bo Zhang

      • Abstract
      • Slides

      Background

      Crizotinib is an orally taken tyrosine kinase inhibitor (TKI) targeting both ALK and ROS1 rearrangement, which have defined two different molecular subgroup patients. The aim of the study was to compare the therapeutic efficacy of crizotinib in advanced lung adenocarcinoma patients diagnosed with ALK or ROS1 mutation.

      Method

      Patients diagnosed with ALK (Group A) or ROS1 (Group B) mutation were identified from our standardized registration system. The effectiveness of crizotinib in eligible patients was retrospectively analyzed.

      Result

      A total of 5348 and 4695 patients were screened and 393 (7.3%, 95% CI, 6.6%-8.0%) and 105 (2.2%, 95% CI, 1.8%-2.7%) positive patients were identified among the two groups, respectively. There were 141 and 32 eligible patients were included for survival analysis. The ORR is 53.0% (95% CI, 43.0%-63.0%) in group A, without statistical significance compared with group B (71%, 95% CI, 51.2%-90.4%, P=0.11). Similar result was also observed in terms of DCR (86%, [95% CI, 79.1%-92.9%] vs. 92.0%, [95%, CI, 80.0%-100.0%], P=0.74). The median PFS in group A was 12.4 months (95% CI, 10.2 -14.7 months), which was statistically worse than patients in group B (18.2 months, 95% CI, 6.3 -29.0 months, P=0.02). The OS was too immature to analyze.

      Conclusion

      Patients harboring ROS1 rearrangement derived better prognosis compared with these who had ALK rearrangement when treated with crizotinib.

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      P1.01-30 - Crizotinib in Advanced Non-Adenocarcinoma, NSCLC (NA-NSCLC) Patients with ALK Rearrangement: A Retrospective Study and Literature Review (ID 12942)

      16:45 - 18:00  |  Author(s): Bo Zhang

      • Abstract
      • Slides

      Background

      The aim of the study was to investigate the prevalence of anaplastic lymphoma kinase (ALK) rearrangement in non-adenocarcinoma, non-small cell lung cancer (NA-NSCLC) patients and therapeutic efficacy of crizotinib in these patients.

      Method

      From January 2013 to January 2017, NA-NSCLC patients who were diagnosed with ALK rearrangement were screened. The effectiveness of crizotinib in positive patients was retrospectively analyzed. A literature review was performed and eligible cases were analyzed combined with our data.

      Result

      A total of 1212 NA-NSCLC patients were screened during the period with 25 positive patients identified (2.1%, 95% CI, 1.3%-2.9%). A statistically higher percentage of female patients (40.0% vs. 10.4%, P< 0.01), non-smoker (72.0% vs.43.2%, P< 0.01), containing adenocarcinoma component (36.0% vs. 7.1%, P< 0.01) and advanced stage (68.0% vs. 45.6%, P=0.03) were observed in ALK positive group. The median PFS of the 9 eligible patients in our institution was 7.0 months (95% CI, 0-15.6 months). We combined our data with the sporadic cases from 10 previous case reports (total n=19) and found that the median PFS was 7.0 months (95% CI, 5.6-8.4 months).

      Conclusion

      Our study suggested the opportunity to test ALK rearrangement in NA-NSCLC patients, especially in female, non-smoker and patients containing adenocarcinoma component. Crizotinib provides an option for the treatment of NA-NSCLC patients who diagnosed with ALK rearrangement.

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    P2.03 - Biology (Not CME Accredited Session) (ID 952)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.03-22 - OCT4&amp;SOX2 Specific CTLs Plus PD-1 Inhibitor Had Synergistic Effect on Killing CSC And Treating Drug-Resistant Lung Cancer Mice (Now Available) (ID 12402)

      16:45 - 18:00  |  Author(s): Bo Zhang

      • Abstract
      • Slides

      Background

      This study aimed to investigate the synergistic effect of OCT4&SOX2 specific cytotoxic T lymphocytes (CTLs) and PD-1 inhibitor on killing lung cancer stem-like cells (LCSCs) and their efficacy in treating drug-resistant lung cancer (DRLC) mice.

      Method

      OCT4&SOX2 specific CTLs and PD-1 inhibitor with differed doses were applied to treat PC9 cells and PC9 LCSCs. CCK8 assay and flow cytometry (FCM) assay with CFSE staining target cells before treatment and PE staining died cells after treatment were conducted to detect the cytotoxic activity. DRLC mice were constructed by injection of PC9 LCSCs suspension and Matrigel into left lung of SD mice. DRLC mice was randomly divided into 5 group: Control group, CMV pp65 CTLs group, OCT4&SOX2 CTLs group, PD-1 inhibitor group and OCT4&SOX2 CTLs+PD-1 inhibitor group.

      Result

      In vitro, Both CCK8 assay and FCM assay disclosed that OCT4&SOX2 specific CTLs plus PD-1 inhibitor presented with elevated cytotoxic activity on PC9 cells and PC9 LCSCs. In vivo, tumor volume and tumor weight were decreased, while tumor necrosis and tumor apoptosis were increased in OCT4&SOX2 CTLs group than CMV pp65 CTLs group and control group, and in OCT4&SOX2 CTLs+PD-1 inhibitor group than OCT4&SOX2 CTLs group and PD-1 inhibitor group. In addition, CD8 expression was increased while OCT4 and SOX2 expressions were decreased in OCT4&SOX2 CTLs+PD-1 inhibitor group than OCT4&SOX2 CTLs group and PD-1 inhibitor group.

      Conclusion

      In conclusion, OCT4&SOX2 specific CTLs and PD-1 inhibitor presented with synergistic effect on killing LCSCs in vitro and treating DRLC mice in vivo.

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