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Jianxing He



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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): Jianxing He

      • 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): Jianxing He

      • 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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    MA01 - Novel Systemic Treatment in NSCLC (ID 102)

    • Event: WCLC 2020
    • Type: Mini Oral
    • Track: Antibody Drug Conjugates, Novel Therapeutics and Cytotoxics
    • Presentations: 1
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      MA01.04 - A Randomized Study Comparing Cisplatin/Paclitaxel Liposome vs Cisplatin/Gemcitabine in Chemonaive, Advanced Squamous NSCLC (ID 1225)

      11:45 - 12:45  |  Author(s): Jianxing He

      • Abstract

      Introduction

      Platinum-based chemotherapy is still the backbone of advanced squamous non–small-cell lung cancer (NSCLC). Paclitaxel (PTX) liposome is the only PTX liposomal formulation on the market for the treatment of lung, ovarian and breast cancer since 2006 in China. The purpose of this study was to compare the clinical efficacy and safety between PTX liposome/cisplatin and gemcitabine/cisplatin as first-line treatment of patients with staged IIIB/IV squamous NSCLC.

      Methods

      Eligible patients with chemo naive, advanced, squamous NSCLC were randomized to receive PTX liposome (175 mg/m2, on day 1) and cisplatin (75 mg/m2 on day 1, LP group) or gemcitabine (1,000 mg//m2, on day 1 and 8) and cisplatin (75 mg/m2 on day 1, GP group) intravenously, every 3 weeks for 4-6 cycles. Primary end point of the study was progression-free survival(PFS).

      Results

      A total of 540 patients from 34 centers of China were enrolled. Median age: 64.5 years; male/ female: 497(93.1%)/37(/6.9%); stage IIIB/IV: 177(33.1%)/357(66.9%) and ECOG PS 0/1: 87(16.3%)/447(83.7%). After a median follow-up of 15.4 months, PFS and overall survival were not different between LP and GP groups (median PFS 5.2 vs. 5.5 months, hazard ratio [HR] 1.03, P=0.5762; median OS 14.6 vs 12.5 months, HR 0.83, P=0.2147). Overall response rate was comparable between the 2 groups, 41.8% in LP group vs 45.9% in GP group. The most common adverse events (AEs) in the both groups were anemia, neutropenia, leukopenia and thrombocytopenia. AEs of grade 3 or higher occurred in 68.3% of the patients in the LP group and in 66.5% of the patients in the GP group. Grade 3 or higher anemia (31.2%, 84/269 vs. 14.3%, 38/265, P<0.0001) and thrombocytopenia (14.1%, 38/269 vs. 1.5%, 4/265, P<0.0001) were more frequent in the GP group, whereas grade 3 or higher neutropenia (35.5%, 94/265 vs. 28.3%, 76/269, P=0.0781) and leukopenia (23.4%, 62/265 vs. 19.0%, 51/269, P=0.2438) were more frequent in the LP group. Discontinuation of treatment due to AEs was more frequent in the GP group than in LP group (26.4% vs. 10.9%, P<0.0001).

      Conclusion

      The chemo-regimens, LP and GP produce comparable efficacy in terms of ORR, PFS and OS as 1st line therapy of advanced squamous NSCLC. But, LP is well tolerated and results in less frequent of anemia and thrombocytopenia and lower discontinuation of treatment in Chinese patients. So, LP is one of standard 1st line chemotherapy for advanced squamous NSCLC patients. (ClinicalTrials.gov number, NCT02996214)

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    MA12 - Controversies Old and New (ID 230)

    • Event: WCLC 2020
    • Type: Mini Oral
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
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      MA12.11 - What Regimen Should Be Chosen for Pulmonary Large Cell Neuroendocrine Carcinoma? A Systemic Review and Meta-Analysis (ID 667)

      16:45 - 17:45  |  Author(s): Jianxing He

      • Abstract

      Introduction

      Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare type of lung cancer which shares many similarities with small cell lung cancer (SCLC). No consensus on the choice of both first-line and adjuvant chemotherapy regimen for LCNEC patients. A systematic review and meta-analysis were performed to evaluate outcomes of LCNEC patients on different regimens.

      Methods

      A review of studies was performed on electronic databases and other sources to identify publications on comparative prognostic outcomes of SCLC and NSCLC regimen in LCNEC patients. Endpoints included hazard ratios of overall survival (OS) and progression-free survival (PFS).

      Results

      Six relevant studies with 7 comparative results from SCLC versus NSCLC regimen were identified. A total of 446 patients were eligible for analysis. Among them, 213 and 42 in first-line and adjuvant chemotherapy underwent NSCLC regimen. Meanwhile, 165 and 26 patients received SCLC regimen were in the corresponding comparisons. SCLC regimen could improve OS (HR 0.73, 95%CI 0.58-0.92) and PFS (HR 0.68, 95%CI 0.54-0.85) in first-line patients than NSCLC regimen. Same result was also observed in adjuvant chemotherapy (HR 0.03, 95%CI 0.02-0.07).

      Study Year Type Primary endpoint Sample size Stage Type of study
      Rossi 2005 First-line/Adjuvant OS 82 I-IIIB Retrospective
      Sun 2012 First-line OS, PFS 45 IV Retrospective
      Naidoo 2016 First-line OS 49 IV Retrospective
      Derks 2017 First-line or above OS, PFS 128 IV Retrospective
      Eldessouki 2018 First-line OS 15 I-IV Retrospective
      Zhang 2019 Fist-line/Adjuvant OS, PFS 381 I-IV Retrospective


      figure 3.jpg

      figure 2.jpg

      Conclusion

      The present meta-analysis indicated LCNEC patients received SCLC regimen had improved OS and PFS both in first-line and adjuvant treatments compared to NSCLC regimen.

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    P04 - Early Stage/Localized Disease - Perioperative Therapy (Neoadjuvant Therapy, Surgery, Adjuvant Therapy) (ID 113)

    • 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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      P04.12 - A Novel Lung Autotransplantation Technique for Treating Central Lung Cancer and Bronchial Malignancy (ID 1627)

      00:00 - 00:00  |  Author(s): Jianxing He

      • Abstract

      Introduction

      Lung autotransplantation is an alternative technique in treating central lung cancer for the patients who are not allowed to receive pneumonectomy with poor pulmonary function. We hereby reported a novel lung autotransplantation technique for treating central NSCLC and bronchial malignancy. The feasibility and potential superiority were also discussed.

      Methods

      Two cases of central NSCLC involving right main bronchus were received right basal segment and right lower lobe autotransplantation, respectively. Inferior pulmonary vein of graft was reconnected to superior pulmonary vein in both cases. One case received anastomosis of basal segment artery and anterior segment artery, while the other case received pulmonary artery angioplasty. Both procedures were performed in situ without graft perfusion. The airway reconstructions were completed via end-to-side anastomosis of graft bronchus and lateral wall of trachea instead of end-to-end reconnection with main bronchus.

      Results

      Both patients were transferred to ICU postoperatively for further management. One patient was ventilated with endotracheal intubation. He was extubated on postoperative day (POD) 2 and transferred to normal ward on POD 4. The other patient was extubated in post-anesthetic recovery room and transferred to normal ward on POD 4. Their chest tubes were successfully removed within 7 days. They were eventually discharged within 11 days postoperatively. No severe complication, including severe infection, anastomosis rupture, atelectasis, embolism or anastomosis was observed during the postoperative follow-up.auto 1.pngautotransplantation1.png

      Conclusion

      This end-to-side bronchiotracheal reconstruction technique is feasible for treating central NSCLC and bronchial malignancy. By simplifying the anastomosis process, it may be more efficient and less time-consuming than ordinary method.

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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): Jianxing He

      • 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): Jianxing He

      • 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): Jianxing He

      • 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): Jianxing He

      • 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.

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    P47 - Small Cell Lung Cancer/NET - Biology / Translational (ID 234)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P47.12 - Does Pulmonary Adenocarcinoma With Neuroendocrine Differentiation Deserve A New Classification? (ID 728)

      00:00 - 00:00  |  Author(s): Jianxing He

      • Abstract

      Introduction

      Pulmonary neuroendocrine tumor (NET) is a category of lung cancers characterized as neuroendocrine features with low incidence and poor prognosis. Unlike other NETs, little was known about adenocarcinoma with neuroendocrine differentiation (ANED) because of its rarity. A large-scale study was performed to investigate the clinical features, treatments and survival outcomes of ANED.

      Methods

      All cases of primary ANED, SCLC and LCNEC were identified from the SEER database from 2004 to 2016. The clinical features and treatments of ANED were described and studied.

      Results

      A total of 37608 patients were included. Only 214 cases of ANED were recorded. Half of ANEDs were poor differentiated. The preferent site was upper lobe. Most patients were diagnosed as IIIB-IV stages. The outcomes of ANED were similar to LCNEC which were better than SCLC in stage I. In advanced stages, no difference was observed. Patients received adjuvant chemotherapy had better OS in IA-IB. Same trends could be observed in IIA-IV patients.

      layout 1.jpglayout 3.jpg

      Clinical featurss

      ANED

      (N = 214)

      LCNEC

      (n = 2257)

      SCLC

      (n=35137)

      Age, years

      Mean (SD)

      66.2 (10.8)

      65.4 (10.4)

      66.7 (10.1)

      Gender, No. (%)

      Male

      123 (57.5)

      1246 (55.2)

      17674 (50.3)

      Female

      91 (42.5)

      1011 (44.8)

      17463 (49.7)

      Race, No. (%)

      White

      153 (63.5)

      1789 (79.3)

      28895 (82.2)

      Black

      32 (15.0)

      272 (12.1)

      3247 (9.3)

      Asian

      12 (5.6)

      77 (3.4)

      1238 (3.5)

      Other

      17 (7.9)

      119 (5.2)

      1757 (5.0)

      Tumor size(mm)

      Mean (SD)

      51.5 (58.9)

      45.9 (42.2)

      53.1 (42.0)

      Grade, No. (%)

      Well;

      2 (0.9)

      11 (0.5)

      65 (0.2)

      Moderately;

      22 (10.3)

      32 (1.4)

      142 (0.4)

      Poorly;

      116 (54.2)

      859 (38.1)

      3311 (9.4)

      Undifferentiated;

      6 (2.8)

      263 (11.7)

      6501 (18.5)

      Unknown

      68 (31.8)

      1092 (48.3)

      25118 (71.5)

      Stage, No. (%)

      IA

      27 (12.6)

      351 (15.6)

      972 (2.8)

      IB

      18 (8.4)

      269 (11.9)

      943 (2.7)

      IIA

      8 (3.7)

      104 (4.6)

      632 (1.8)

      IIB

      13 (6.1)

      111 (4.9)

      574 (1.6)

      IIIA

      33 (15.4)

      259 (11.5)

      4750 (13.5)

      IIIB

      25 (11.7)

      169 (7.5)

      5219 (14.9)

      IV

      90 (42.1)

      994 (44.0)

      22047 (62.7)

      Surgery, No. (%)

      No surgery

      138 (64.5)

      1301 (57.6)

      33953 (96.6)

      Surgery

      76 (35.5)

      956 (42.4)

      1184 (3.4)

      Chemotherapy, No. (%)

      No radiation

      181 (84.6)

      1883 (83.4)

      31543 (89.8)

      Radiation

      33 (15.4)

      374 (16.6)

      3594 (10.2)

      Chemotherapy, No. (%)

      No/Unknown

      99 (46.3)

      1063 (47.1)

      9549 (27.2)

      Yes

      115 (53.7)

      1194 (52.9)

      25588 (72.8)

      Conclusion

      Adenocarcinoma with neuroendocrine differentiation is has similar outcomes as LCNEC in various stages. Surgery with adjuvant chemotherapy could improve survival in Stage I ANED and might bring benefit to advanced stage patients. It could be included in LCNEC and might not need a new clinical classification.

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    P62 - Tumor Biology and Systems Biology - Basic and Translational Science - Metabolomics (ID 200)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Tumor Biology and Systems Biology - Basic and Translational Science
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P62.10 - Rhophilin-2 Upregulates Glutamine Synthetase by Stabilizing c-Myc Protein and Confers Resistance to Glutamine Deprivation in Lung Cancer (ID 1865)

      00:00 - 00:00  |  Author(s): Jianxing He

      • Abstract

      Introduction

      RHPN2, a member of rhophilin family of rho-binding proteins, regulates actin cytoskeleton and vesicular trafficking, and promotes mesenchymal transformation in cancer. We have found that RHPN2 was significantly mutated in lung adenocarcinoma (LUAD). however, the role of RHPN2 in lung cancer is not fully understood.

      Methods

      In the present study, we investigated the expression of RHPN2 in 125 patients with LUAD by qRT-PCR and correlated its expression with clinical characteristics. The effects of RHPN2 on the proliferation and invasion of lung cancer cells were determined by CCK-8 and in vitro transwell assays, clonogenic assay, and xenograft mouse model. The RhoA pull down assay and Western blotting were performed to elucidate the mechanism of RNPN2 in tumorigenesis of lung cancer.

      Results

      RHPN2 was overexpressed in tumors from LUAD, and high levels of RHPN2 were associated with poor prognosis of LUAD patients. RHPN2 was required for proliferation and invasion of lung cancer cells. Intriguingly, overexpression of RHPN2 confers the resistance to glutamine depletion in lung cancer cells. Mechanistic studies revealed that ectopic overexpression of RHPN2 promoted the stability of c-Myc protein and increased c-Myc target glutamine synthetase (GS). Analysis of GS expression in clinical sample showed that the expression of GS was elevated in tumor cells. Kaplan-Meier analysis revealed that high levels of GS were significantly associated with worse overall survival time of the patients with LUAD.

      figure 1 overexpression of rhpn2 is associated with worse clinical outcome of patients with lung adenocarcinoma.png

      Conclusion

      Taken together, this study suggested that RHPN2 was involved in tumorigenesis of lung cancer via modulating c-Myc stability and the expression of its target GS in lung adenocarcinoma, which links RHPN2 and glutamine metabolism.

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    P83 - Immunotherapy (Phase II/III Trials) - Immunotherapy Plus Targeted Therapy (ID 260)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Immunotherapy (Phase II/III Trials)
    • Presentations: 2
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P83.01 - Updated Survival and Biomarker Analysis of Camrelizumab and Apatinib in Previously Treated pts of Advanced Non-Squamous NSCLC (ID 1657)

      00:00 - 00:00  |  Author(s): Jianxing He

      • Abstract

      Introduction

      Our previous report showed that camrelizumab combination with apatinib have showed promising results in previously chemotherapy-treated patients with advanced non-squamous NSCLC. We further report the updated survival data and biomarkers analysis here.

      Methods

      1.jpgWe conduct a multi-center single-arm phase 1b/II study investigating the safety and efficacy of camrelizumab and apatinib in previously treated patients with advanced NSCLC. This study included phase 1b apatinib dose escalation phase and phase II population expansion cohort. The primary endpoints were safety and ORR respectively. Patients of non-squamous NSCLC who received apatinib 250 mg orally once daily in combination with camrelizumab 200 mg intravenously on day 1 every 2 weeks were included into this analysis (NCT03083041). 22C3 array was used for PD-L1 immunohistochemistry and OseqTM-pan cancer panel (including 636 genes and 1.95Mb) was used for the genomic alternation testing.

      Results

      Between March 21, 2017 and October 11, 2018, 105 patients were enrolled, 91patients had PD-L1 expression testing and 46 had sufficient tissue for NGS. As the cutoff of Aug 15, 2019, one had a confirmed complete response, 28 had confirmed partial response, and 48 had stable disease, ORR was 30.9% (29/94, 95% CI, 21.7-41.2%) in the efficacy-evaluable population (n=94). Median progression-free survival was 5.7 months (95% CI, 4.5–8.8) and median overall survival was 19.2 months (95% CI, 11.2-24.5) in all patients. PD-L1 expression was positive in 25(27.4%) patients, median TMB is 9 mutations/Mb, while STK11 and KEAP1 mutation were found in 7 and 10 patients respectively. Patients with PD-L1 TPS>1% and high TMB could not predict higher ORR (36.0% vs 22.7%, P = 0.20; 29.2% vs 36.4%, p=0.564, respectively) or longer PFS (median 6.8 vs 5.1 months, P = 0.61; 7.8 vs 8.0 months, P = 0.98). Notably, patients with STK11/KEAP1 mutation had a numerically higher ORR (42.9% vs 28.1%, P =0.327), longer PFS (median 9.4 vs 5.3, P = 0. 592) and statistically significantly longer OS (median NR vs NR, P = 0. 047) than those of wild type. The most common treatment-related adverse events of grade 3 or higher were hypertension (18 [17.1%]), palmar-plantar erythrodysesthesia syndrome (14 [13.3%]), and increased gamma-glutamyltransferase (10 [9.5%]).

      Conclusion

      Combined camrelizumab and apatinib had promising antitumor activity and acceptable safety in previously treated patients with advanced non-squamous NSCLC, especially in these with STK11 or KEAP1 mutation, phase III trial is ongoing for further validation (NCT04203485).

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      P83.03 - Efficacy of Camrelizumab (SHR-1210) Plus Apatinib in Advanced NSCLC with EGFR Mutation (ID 1864)

      00:00 - 00:00  |  Author(s): Jianxing He

      • Abstract

      Introduction

      Treatment options are still limited for pts with advanced EGFR mutated NSCLC and resistant to EGFR-TKI. Here, we reported preliminary efficacy and safety of PD-1 camrelizumab (SHR-1210) plus apatinib in pts with EGFR mutation.

      Methods

      In this open-label, multi-center phase Ib/II study, pts aged 18-70 years, with EGFR mutation, and had disease progression on or after one line of platinum-based chemotherapy and at least one kind of EGFR-TKI were enrolled in dose escalation phase Ib and in dose expansion phase II. All pts received apatinib 250mg orally once daily plus camrelizumab 200mg every two weeks until disease progression or intolerable toxicity ( NCT03083041). Primary endpoint was objective response rate (ORR). Exploratory analyses of response and survival were conducted in pts classified by EGFR mutation types.

      Results

      Between Nov, 2017 and Jan, 2019, 40 NSCLC pts (3 in phase Ib and 37 in phase II) with EGFR mutation were enrolled. As the cutoff of December 15, 2019, the median follow-up was 10.8 months (range, 0.5-18.6). Four pts were still receiving treatment at the time of analysis. Among all 40 pts, 22 (55.0%) had EGFR 19 deletion (19del), 14 (35.0%) had L858R mutation, and 3 (7.5%) had EGFR 20 insertion (20ins). ORR was 20.0% (8/40, 95% CI, 9.1%-35.6%) and disease control rate (DCR) 62.5% (25/40, 95% CI, 45.8%-77.3%) in the whole population. Median duration of response was not reached (95% CI, 3.5-NR), median progression-free survival (mPFS) was 3.2 months (95% CI, 1.5-6.4m), and overall survival was not reached. Subgroup analysis showed that the ORR in pts with EGFR 20ins (n=3) or EGFR L858R(n=14) was higher than those with EGFR 19del (n=22) (33.3% vs. 21.4% vs. 13.6%, p=0.65). Similarly, longer mPFS was seen in pts with EGFR 20ins or L858R than in those with EGFR 19del (8.3m vs. 5.4m vs. 2.8m, p=0.94) . The most common treatment-related adverse events of grade 3 or higher were hypertension (7 [16.3%]), proteinuria (5 [11.6%]), palmar-plantar erythrodysesthesia syndrome (4 [9.3%]), and hypertriglyceridemia (3 [7.0%]).

      Table 1. Efficacy of camrelizumab and apatinib combination treatment in advanced NSCLC pts with EGFR mutation

      Pts

      ORR

      DCR

      mPFS (mos)

      mOS (mos)

      All pts

      40

      20.0%

      62.5%

      3.2

      NR

      EGFR 19del

      22

      13.6%

      59.1%

      2.8

      NR

      EGFR L858R

      14

      21.4%

      64.3%

      5.4

      NR

      EGFR 20ins

      3

      33.3%

      66.7%

      8.3

      NR

      Conclusion

      Camrelizumab plus apatinib showed a moderate benefit in pts with EGFR mutated NSCLC and showed better efficacy in pts with EGFR 20ins or L858R mutation sub-types, warrant further investigation.