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Wenhua Liang



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    FP14 - Targeted Therapy - Clinically Focused (ID 252)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP14.11 - Icotinib versus Chemotherapy as Adjuvant Treatment for Stage II–IIIA EGFR-Mutant NSCLC (EVIDENCE): A Randomized, Open-Label, Phase 3 Study (ID 3605)

      00:00 - 00:00  |  Author(s): Wenhua Liang

      • Abstract

      Introduction

      Recent studies have shown significant benefits of EGFR tyrosine kinase inhibitors in the adjuvant setting for patients with EGFR-mutant stage IB–IIIA resected NSCLC. This study aimed to compare the efficacy and safety of icotinib with standard chemotherapy in adjuvant setting in patients with EGFR mutant stage II-IIIA NSCLC.

      Methods

      In this randomized, open-label, phase 3 study, eligible patients aged 18-70 years who had completely resected (R0), stage II-IIIA EGFR-mutant NSCLC (in-frame deletion in exon 19 or Leu858Arg point mutation in exon 21) were randomly assigned, in a 1:1 ratio, to receive either adjuvant icotinib (125 mg thrice daily administered orally for 2 years) or four-cycle chemotherapy (cisplatin plus vinorelbine, or cisplatin plus pemetrexed for non-squamous carcinoma). Patients were stratified by clinical stage (II vs IIIA), EGFR mutation type (exon 19 vs 21), and resection methods (lobectomy vs pneumonectomy). The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety.

      Results

      A total of 365 patients were screened, and 322 patients (161 for each arm) were enrolled from 29 centers across China between June 2015 and July 2019. Thirty-nine patients had major protocol violations and were excluded, leaving 283 patients in full analysis set (151 in icotinib arm and 132 in chemotherapy arm, respectively). 53% and 47% of patients had an EGFR mutation of 19 Del and 21 L858R, respectively. At the data cutoff (March 31, 2020) for the pre-specified interim analysis, 98 out of 196 (50%) events were recorded with a median follow-up of 24.9 months (95% CI, 22.1 to 28.8). In full analysis population, the median DFS (mDFS) was 47.0 months (95% CI, 36.44 to not reached) in the icotinib group and 22.1 months (95% CI, 16.8 to 30.4) in the chemotherapy group (stratified hazard ratio=0.36; 95% CI, 0.24 to 0.55; P < 0.0001). Analyses of DFS based on stratification criteria and vital demographic and prognostic factors showed consistent benefits of icotinib treatment across subgroups. The 3-year DFS was 63.9% in the icotinib group and 32.5% in the chemotherapy group. It is immature to perform OS analysis with14 (9.3%) patients in the icotinib group and 14 (10.6%) patients in the chemotherapy group died, respectively. Adverse events of grade 3 or 4 were observed in 10.9% of the patients in the icotinib group and 61.2% in the chemotherapy group. Treatment-related serious adverse events occurred in 2 (1.3%) patients in the icotinib group and 19 (13.7%) patients in the chemotherapy group. No interstitial pneumonia or treatment-related death was observed in each group.

      Conclusion

      Adjuvant icotinib significantly improved DFS in patients with EGFR mutant stage II-IIIA NSCLC compared with standard chemotherapy and demonstrated a better tolerability profile. Icotinib can provide a new treatment option for stage II-IIIA NSCLC patients with activating EGFR mutation.

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    JICC01 - Joint IASLC-CAALC-CSCO Session: The Truth and Myth of Oral Anti-VEGFR Inhibitors for Advance NSCLC (ID 276)

    • Event: WCLC 2020
    • Type: Workshop
    • Track: N.A.
    • Presentations: 1
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      JICC01.11 - Icotinib versus Chemotherapy as Adjuvant Treatment for Stage II–IIIA EGFR-Mutant NSCLC (EVIDENCE): A Randomized, Open-Label, Phase 3 Study (ID 4275)

      07:00 - 09:00  |  Author(s): Wenhua Liang

      • Abstract

      Introduction
      Recent studies have shown significant benefits of EGFR tyrosine kinase inhibitors in the adjuvant setting for patients with EGFR-mutant stage IB–IIIA resected NSCLC. This study aimed to compare the efficacy and safety of icotinib with standard chemotherapy in adjuvant setting in patients with EGFR mutant stage II-IIIA NSCLC. Methods
      In this randomized, open-label, phase 3 study, eligible patients aged 18-70 years who had completely resected (R0), stage II-IIIA EGFR-mutant NSCLC (in-frame deletion in exon 19 or Leu858Arg point mutation in exon 21) were randomly assigned, in a 1:1 ratio, to receive either adjuvant icotinib (125 mg thrice daily administered orally for 2 years) or four-cycle chemotherapy (cisplatin plus vinorelbine, or cisplatin plus pemetrexed for non-squamous carcinoma). Patients were stratified by clinical stage (II vs IIIA), EGFR mutation type (exon 19 vs 21), and resection methods (lobectomy vs pneumonectomy). The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. Results
      A total of 365 patients were screened, and 322 patients (161 for each arm) were enrolled from 29 centers across China between June 2015 and July 2019. Thirty-nine patients had major protocol violations and were excluded, leaving 283 patients in full analysis set (151 in icotinib arm and 132 in chemotherapy arm, respectively). 53% and 47% of patients had an EGFR mutation of 19 Del and 21 L858R, respectively. At the data cutoff (March 31, 2020) for the pre-specified interim analysis, 98 out of 196 (50%) events were recorded with a median follow-up of 24.9 months (95% CI, 22.1 to 28.8). In full analysis population, the median DFS (mDFS) was 47.0 months (95% CI, 36.44 to not reached) in the icotinib group and 22.1 months (95% CI, 16.8 to 30.4) in the chemotherapy group (stratified hazard ratio=0.36; 95% CI, 0.24 to 0.55; P < 0.0001). Analyses of DFS based on stratification criteria and vital demographic and prognostic factors showed consistent benefits of icotinib treatment across subgroups. The 3-year DFS was 63.9% in the icotinib group and 32.5% in the chemotherapy group. It is immature to perform OS analysis with14 (9.3%) patients in the icotinib group and 14 (10.6%) patients in the chemotherapy group died, respectively. Adverse events of grade 3 or 4 were observed in 10.9% of the patients in the icotinib group and 61.2% in the chemotherapy group. Treatment-related serious adverse events occurred in 2 (1.3%) patients in the icotinib group and 19 (13.7%) patients in the chemotherapy group. No interstitial pneumonia or treatment-related death was observed in each group. Conclusion
      Adjuvant icotinib significantly improved DFS in patients with EGFR mutant stage II-IIIA NSCLC compared with standard chemotherapy and demonstrated a better tolerability profile. Icotinib can provide a new treatment option for stage II-IIIA NSCLC patients with activating EGFR mutation.

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    P08 - Early Stage/Localized Disease - Epidemiology (ID 117)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Early Stage/Localized Disease
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P08.02 - Lung Cancer Risk in Liver Transplant Recipients: A Meta-Analysis (ID 1604)

      00:00 - 00:00  |  Author(s): Wenhua Liang

      • Abstract

      Introduction

      Patients underwent liver transplantation are considered to be associated with an increased risk of developing cancers. We performed a meta-analysis to determine whether there was an increased risk of lung cancer in liver transplant recipients.

      Methods

      PubMed, Web of Science, EMBASE, Medline were searched. Random-effects model meta-analyses were used to calculate standardized incidence ratios (SIRs) for liver transplant recipients versus the general population. Subgroup analyses were performed based on country/region of each study.

      Results

      Based on data from 552 998 patients, we identified a 1.88 -fold higher SIR [95% confidence intervals (CI) 1.60-2.22, P<0.001] of lung cancer in liver transplantation recipients, compared with the general population. In subgroup analyses, we found that the order of lung cancer SIR after liver transplantation was consistent among different ethnic groups, and Asian countries had the highest SIRs compared with European and North American countries, while Oceanian countries had the lowest SIRs (Figure 1).graph.png

      Conclusion

      Our study demonstrated that liver recipients showed a significantly greater risk of lung cancer, which varied among different ethnic groups. Such association can provide guidance for clinicians in the detection of lung cancer among liver transplantation recipients.

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    P42 - Screening and Early Detection - Risk Modelling and Artificial Intelligence (ID 177)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Screening and Early Detection
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P42.08 - Association Between the Age at First-Live Birth and Lung Cancer Risk: Meta-Analysis and Mendelian Randomization Analysis (ID 1921)

      00:00 - 00:00  |  Author(s): Wenhua Liang

      • Abstract

      Introduction

      Evidence about the role for reproductive factors in the etiology of lung cancer in women is conflicting. What’s more, the causality of such association is uncertain since conventional observational studies are easily influenced by confounders and inverse causation. Therefore, we carried out this meta-analysis and Mendelian randomization (MR) analysis in order to examine whether the age of first-live birth is associated with lung cancer risk.

      Methods

      Both meta-analysis and MR analysis were conducted in our study. For meta-analysis, a comprehensive search was performed in online database up to March 2020 and the risk of lung cancer was identified by calculating the relative ratios (RR) and its 95% confidence interval (CI). For MR studies, six relevant single nucleotide polymorphisms (SNPs) identified by latest genome-wide association studies (GWAS) were used as instrumental variables (IVs) in our study. Summary data of genetic information were obtained from three studies of the International Lung Cancer Consortium (ILCCO). Inverse-weighted (IVW) method was applied to estimate the causation between them.

      Results

      The results of meta-analysis showed women with older age at first-live birth (RR=0.93, 95%CI= 0.80-1.08, p=0.328) (Figure A) had a trend towards decreased risk of lung cancer without statistical significance. Furthermore, the results of IVW methods also demonstrated that older age at first-live birth of women was causally associated with decreased risks of both overall lung cancer (OR=0.82, 95%CI= 0.69-0.97, p=0.017) (Figure B) and adenocarcinoma (OR=0.75, 95%CI= 0.59-0.97, p=0.029). However, such association was not observed in squamous cell lung cancer (OR=0.77, 95%CI= 0.57-1.05, p=0.103).

      figure a.jpgfigure b.jpg

      Conclusion

      Older age at first-birth of women seemed to be a protective factor for lung cancer, suggesting a role of reproductive factors in the development of lung cancer. Future studies on reproductive factors and lung cancer risk are warranted.

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    P43 - Screening and Early Detection - Biomarkers (ID 178)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Screening and Early Detection
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P43.05 - No Causal Association is Found Between C-Reactive Protein and Lung Cancer Risk: A Mendelian Randomization (ID 2259)

      00:00 - 00:00  |  Author(s): Wenhua Liang

      • Abstract

      Introduction

      Significantly rising of the plasma concentration of circulating C-reaction proteins (CRP) is pervasive in the progress of lung cancer, which shows the compact relationship between both symptoms. However, the results of the associations between CRP and lung cancer risk vary across different cohort studies. Observational studies are susceptible to potential confounders or reverse causality and their relationship remains uncertain. With a Mendelian randomization (MR) approach, we were able to investigate the causal relationship between genetically elevated CRP concentration and lung cancer risk.

      Methods

      Individual-level genetic summary date data of 11 807 lung cancer cases and 81 5494 controls from 13 participating studies in three international consortia were used, including the International Lung Cancer Consortium (ILCCO), Neale Lab and MRC-IEU. Our study included 22 single nucleotide polymorphisms (SNPs) as instrumental variables which previously association with CRP concentration. Inverse-weighted (IVW) method was applied to estimate the causal relationship between genetically elevated CRP concentration and lung cancer risk. To further evaluate the pleiotropy, weighted median and MR-Egger regression method were implemented as well. Subgroup analyses according to different histological subtypes and malignant sites of lung cancer were also conducted.

      Results

      The demonstration of IVW study did not reveal the causal relationship shared across CRP and lung cancer overall [odds ratio (OR) = 1.000; 95% confidence interval (CI) =1.000-1.000, p = 0.071](Table 1). Meanwhile, no association was found among the subgroups.

      table 1-.jpg

      Conclusion

      Our study indicated that CRP concentration is unlikely to be casual factor risk factor in the development of lung cancer though several subgroups were examined using adequate quantities of statistical data. Still, it opens up a new concept for the current research orientation, that the further investigation of the deep relationship between both symptoms is required to be unveiled in pathologic and biochemistry aspects.

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    P44 - Screening and Early Detection - Association of Lung Cancer with other Chronic Diseases (ID 180)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Screening and Early Detection
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P44.01 - Menstruation and Lung Cancer Risk: A Meta-Analysis and a Mendelian Randomization Study (ID 1710)

      00:00 - 00:00  |  Author(s): Wenhua Liang

      • Abstract

      Introduction

      It was not clear whether women’s menstruation would affect the risk of lung cancer. We therefore conducted a meta-analysis and further performed a two-sample Mendelian randomization (TSMR) to explore the relationship between women’s menstruation and lung cancer.

      Methods

      Cochrane Central Register of Controlled Clinical Trials, PubMed, Web of Science, EMBASE, Medline as well as major conference proceedings were systematically searched. We selected age of menarche, age of menopause and menstrual cycle to represent individual women’s menstruation.

      Relative Risk (RR) of lung cancer specific incidence were synthesized using random effects model. A dose-response was also conducted to analyze the trend of different age of menarche and menopause. A TSMR with 776,767 samples was carried out to reveal the causal relationship between menstrual factors and lung cancer at genetic level.

      Results

      Sixteen studies involving 602,286 participants were included. The mean age at enrollment was 61.37±4.7 with 9,694 lung cancer cases. Result of meta-analysis showed that the later of the menarche and menopause, the longer of the menstrual cycle had a lower risk of lung cancer (age of menarche: RR: 0.84, 95% Cl: 0.72-0.97, p=0.021; age of menopause: RR: 0.72, 95% Cl: 0.59-0.88, p=0.001; length of menstrual cycle: RR: 0.99, 95% Cl: 0.71-1.38, p=0.943). Result of Mendelian randomization also showed similar correlations between menstruation and lung cancer (age of menarche: OR: 0.54, 95% Cl: 0.40-0.73, p<0.001; age of menopause: OR: 0.90, 95% Cl: 0.84-0.96, p=0.01; length of menstrual cycle: OR: 0.61, 95% Cl: 0.38-0.98, p=0.04).

      figure.1.jpg

      Conclusion

      Our study demonstrated that the later women's menarche and menopause time means lower lung cancer risk, who causality is confirmed at the genetic level. We also provide evidence for a potential causal association of menstrual cycle with decreased of lung cancer.