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Lele 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: 1
    • 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): Lele 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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    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): Lele 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): Lele 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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    P3.13 - Targeted Therapy (Not CME Accredited Session) (ID 979)

    • 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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      P3.13-09 - ALTER-0303 Study: Tumor Mutation Index (TMI) For Clinical Response to Anlotinib in Advanced NSCLC Patients at 3rd Line (ID 12395)

      12:00 - 13:30  |  Author(s): Lele 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.

      Method

      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.

      Result

      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).

      Conclusion

      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.

      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.