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Yi-long Wu

Moderator of

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    PL05 - Affordable and Accessible Lung Cancer Care (Japanese, Mandarin, Spanish Translation Available) (ID 146)

    • Event: WCLC 2020
    • Type: Plenary
    • Track: N.A.
    • Presentations: 9
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      PL05.01 - Chair (ID 3926)

      18:00 - 20:00  |  Presenting Author(s): Yi-long Wu

      • Abstract

      Abstract not provided

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      PL05.02 - Chair (ID 3927)

      18:00 - 20:00  |  Presenting Author(s): Ross Soo

      • Abstract

      Abstract not provided

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      PL05.03 - Chair (ID 3928)

      18:00 - 20:00  |  Presenting Author(s): Daniel SW Tan

      • Abstract

      Abstract not provided

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      PL05.04 - Chair (ID 3929)

      18:00 - 20:00  |  Presenting Author(s): David Harpole

      • Abstract

      Abstract not provided

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      PL05.06 - Non-Invasive Biomarkers in Lung Cancer Screening: Achievements, Promises and Challenges (ID 3931)

      18:00 - 20:00  |  Presenting Author(s): Luis M Montuenga

      • Abstract

      Abstract

      LDCT-based lung cancer screening efficacy for the reduction of lung cancer deaths at the population level is now an evidence-based reality. The initial seminal papers published by the I-ELCAP consortium showing their data in their non-observational trial and the NLST and NELSON randomized trials have clearly shown the efficacy of this lung cancer early detection strategy in high risk individuals. Nevertheless, there are still limited numbers of lung cancer screening programs worldwide, considering the at-risk population1. The present talk will summarize the potential role of biomarkers to increase the efficacy of LDCT-based lung cancer screening. Biomarkers may improve the effectiveness of screening by (a) refining the selection of persons for screening; (b) providing data indicating whether indeterminate screening-detected nodules are of high or lower risk; and (c) predicting outcome or response to therapy, once a lung cancer has been diagnosed 2. I will summarize some of the available biomarkers that have been developed in the context of lung cancer screening3. I will stress on the need of rigorous and statistically sound validation for clinical utility4 and will present some examples of recently developed biomarkers, one of which is a circulating protein panel, on which we are currently working, which includes complement activation related fragments5. I will also mention an example of affordable prognostic marker for early lung cancer, developed in our lab, based on immune-localization of very few proteins6,7. Finally, I will focus on several recently published technologies of circulating DNA deep sequencing, which pursue highly specific and sensitive non-invasive early detection of either lung cancer or of multiple types of cancer: pan-cancer ctDNA analysis in liquid biopsy8-12. I will comment of the advantages and drawbacks of these highly sophisticated novel technologies from the point of view of affordability and cost-effectiveness.

      (1) Oudkerk et al Nat Rev Clin Oncol, 2020, October 12; (2)Veronese et al Cancers, 2020; 12: 1672;(3) Seijo et al J Thoracic Oncol, 2019; 14:343; (4) Mazzone et al. ATS oficial statement Am J Respir Crit Care Med, 2017; 196: e15; (5) Ajona, Pio et al: in revision; (6) Martinez-Terroba et al J Pathol, 2018; 245:421; (7) Martinez-Terroba et al Thorax, 2019; 74:371;(8) Chabon et al Nature, 2020; 580: 245; (9) Beer TM Am J Manag Care, 2020; 26:S292; (10) Cristiano et al Nature 2019; 570:385; (11) Lennon AM et al Science, 2020; 369:6499; (12) Liu et al Ann Oncol, 2020; 31:745.

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      PL05.07 - Legislating Tobacco Out of Business (ID 3932)

      18:00 - 20:00  |  Presenting Author(s): Wanda de Kanter

      • Abstract

      Abstract not provided

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      PL05.08 - How to Double Cancer Cure Rate by 2025 (ID 3933)

      18:00 - 20:00  |  Presenting Author(s): Giorgio Vittorio Scagliotti

      • Abstract

      Abstract not provided

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      PL05.09 - Cancer Treatment in Asia - What is Available, and Is It Effective Enough? (ID 3934)

      18:00 - 20:00  |  Presenting Author(s): Sumitra Thongprasert

      • Abstract

      Abstract

      Talking about Cancer Treatment in Asia is difficult, because Asia cover from East Asia, Southeast Asia, South Asia and Middle East, thus it’s difficult to demonstrate all region as one. Because of these facts I’ll focus my talk on Southeast Asia and Thailand will be use as a prototype.

      Cancer treatment by itself could be from diagnostic work up till end of life care, so I’ll cover all these aspects as much as possible. First is the diagnosis which will include how to make diagnosis, Second is the treatment option and Third is the outcome of the treatment , Fouth is the barrier of all these factors and Fifth is the care of the lung cancer patients both the availability and accessibility to these treatment options.

      Thus there’re a lot of improvement that need to be done inorder to improve the care of Lung Cancer patient in South east Asia

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      PL05.10 - A TeleTrial Model in Lung Cancer - Improving Access & Outcomes (ID 3935)

      18:00 - 20:00  |  Presenting Author(s): Melanie Jane Poxton

      • Abstract

      Abstract not provided



Author of

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    FP14 - Targeted Therapy - Clinically Focused (ID 252)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 3
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP14.09 - Tepotinib Safety in MET Exon 14 (METex14) Skipping NSCLC: Updated Results from the VISION Trial (ID 821)

      00:00 - 00:00  |  Author(s): Yi-long Wu

      • Abstract
      • Slides

      Introduction

      Tepotinib, a highly selective MET inhibitor, demonstrated durable clinical activity in patients with METex14 skipping NSCLC in the Phase II VISION trial (NCT02864992). Here, we report updated safety data from this ongoing study of the largest prospective population of patients with METex14 skipping NSCLC to date.

      Methods

      Patients with advanced EGFR/ALK wild-type NSCLC and METex14 skipping identified by liquid or tissue biopsy received oral tepotinib 500 mg once daily until disease progression, unacceptable toxicity or withdrawal for other reasons. To manage adverse events (AEs), treatment could be interrupted for up to 21 days or the tepotinib dose could be reduced. AEs were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events v4.03.

      Results

      As of July 1, 2020, 255 patients had received tepotinib for a median of 5.1 months (range 0 to 43.4) and treatment was ongoing in 101 patients (39.6%). Median age was 72.0 years (range 41 to 94), 132 patients (51.8%) were female, 171 (67.1%) were white and 184 (72.2%) had Eastern Cooperative Oncology Group performance status 1. The most common treatment-related AEs (TRAEs) were peripheral edema, nausea, diarrhea, blood creatinine increased, and hypoalbuminemia, which were mostly mild or moderate (table). TRAEs led to dose reduction in 71 patients (27.8%), treatment interruption in 90 patients (35.3%) and discontinuation in 27 patients (10.6%). The most common TRAE leading to treatment modification was peripheral edema (dose reduction in 36 patients [14.1%], treatment interruption in 41 patients [16.1%], and discontinuation in 9 patients [3.5%]). Serious TRAEs were reported for 31 patients (12.2%), of which the most common were pleural effusion (9 patients [3.5%]) and peripheral edema (6 patients [2.4%]). Two patients (0.8%) had TRAEs that led to death: one patient with dyspnea, and one patient with dyspnea and acute respiratory failure. Information on TRAEs in patient subgroups and time to onset, resolution and management of key AEs will be presented.

      N Any grade, n (%) Grade ≥3, n (%)
      TRAEs 255 220 (86.3) 64 (25.1)
      Peripheral edema 255 138 (54.1) 19 (7.5)
      Nausea 255 51 (20.0) 1 (0.4)
      Diarrhea 255 50 (19.6) 1 (0.4)
      Blood creatinine increased 255 45 (17.6) 1 (0.4)
      Hypoalbuminemia 255 37 (14.5) 6 (2.4)

      TRAE, Treatment-related adverse event.

      Conclusion

      In the largest prospective study of patients with NSCLC and METex14 skipping to date, tepotinib was generally well tolerated. Peripheral edema, which is a class effect of MET inhibitors, was generally mild or moderate and considered manageable with tepotinib dose reduction or treatment interruption. Proactive monitoring for edema is recommended, with potential consideration of early or prophylactic conservative management measures (e.g. support stockings, limb elevation and increased physical activity).

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      FP14.12 - Quality of Life and Subgroup Analysis in a Phase 3 Randomized Study of Ensartinib vs Crizotinib in ALK–Positive NSCLC Patients: eXalt3. (ID 3852)

      00:00 - 00:00  |  Presenting Author(s): Yi-long Wu

      • Abstract
      • Slides

      Introduction

      Ensartinib (X-396) is a novel second-generation ALK tyrosine kinase inhibitor (TKI). In a phase 3 study interim analysis, ensartinib showed statistically significant improvement of median PFS over crizotinib in patients with ALK+ NSCLC who were ALK TKI naive or received up to one prior chemotherapy line, including higher efficacy against brain metastases. Ensartinib was well tolerated, with low grade rash, pruritus, edema, and transaminitis as the most frequent treatment-related AEs. Here we plan to present subgroups analyses and the quality of life outputs of the phase 3 eXalt3 study (NCT02767804).

      Methods

      Patients with locally tested ALK+ NSCLC (ITT population) were randomized 1:1 to ensartinib (225 mg QD orally) or crizotinib (250 mg BID orally). No crossover was allowed. Patients were stratified by prior chemotherapy, ECOG PS, brain metastases, and geographic region. The modified ITT (mITT) population was prespecified to include all centrally ALK+ patients by Abbott FISH test. The primary endpoint was blinded independent review committee (BIRC)–assessed progression-free survival (PFS; RECIST v.1.1). Secondary endpoints included overall survival (OS), overall response rate (ORR), and time to treatment failure (TTF) in the brain and patients reported outcomes (PRO). PRO data collection included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30). A linear mixed model for repeated measures was used to analyze change from baseline in the Global Health Status/Quality of Life subscale (GHS/QOL), with a change of greater than or equal to ten points deemed meaningful. Time to symptom deterioration will be presented.

      Results

      In total, 290 patients were randomized (ensartinib [n=143]; crizotinib [n=147]).Median age was 54.1 y, 26% of patients had prior chemotherapy, and 36% of patients had baseline CNS metastases (5% had prior brain radiotherapy). The mITT population included 247 patients (ensartinib [n=121]; crizotinib [n=126]). At the July 1, 2020, data cutoff, 139 BIRC-assessed PFS events (73%) occurred in the ITT population and 119 (63%) in the mITT population. Median PFS was 25.8 months with ensartinib vs 12.7 months with crizotinib (HR, 0.52; P=.0003 by log-rank test) with a median follow-up of 23.8 and 20.2 months in the ITT population. Median PFS was not reached with ensartinib vs 12.7 months with crizotinib in the mITT population (HR, 0.48; P=.0002 by log-rank test). New subgroup analyses in mITT for ensartinib showed a trend for higher efficacy by prior chemotherapy vs no chemotherapy (mPFS NR vs 25.8). Both global health status (GHS) as well as 5 functional and 9 symptom domains within EORTC QLQ-C30 had clinical meaningful improvement over time for ensartinib. Ensartinib delays the time to worsening of GHS with HR =0.83 (95% CI [0.57, 1.20]) vs crizotinib. Complete subgroup analyses (forest plot and multivariate analyisis) will be presented at the conference as well as OS updates. Comprehenive EORTC QLQ-C30 and Lung Cancer Symptom Scale scores will also be reported at the conference.

      Conclusion

      In ALK+ NSCLC patients ensartinib represents a new option in first-line setting. QOLs data support its favorable safety profile. Relevant subgroups analyses to evaluate its clinical impact will be presented at the meeting.

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      FP14.17 - Efficacy and Safety of Pralsetinib in Chinese Patients with Advanced RET Fusion+ Non-Small Cell Lung Cancer after Platinum-Based Chemotherapy (ID 2954)

      00:00 - 00:00  |  Author(s): Yi-long Wu

      • Abstract
      • Slides

      Introduction

      RET fusions have been reported as oncogenic drivers in 1% to 2% of non-small cell lung cancer (NSCLC) patients. Pralsetinib is a highly potent and selective RET kinase inhibitor targeting oncogenic RET alterations. A global phase I/II ARROW study (NCT03037385) has demonstrated broad and durable antitumor activity of pralsetinib in a variety of advanced RET-altered solid tumors. Here we present the efficacy and safety results from the phase II NSCLC extension group that enrolled patients from China sites.

      Methods

      RET fusion+ Chinese NSCLC patients previously treated with platinum-based chemotherapy were enrolled and dosed with pralsetinib 400 mg QD. The primary objectives were to assess the objective response rate (ORR) by blinded independent central review (BICR) per RECIST v1.1 and safety profile in Chinese patients.

      Results

      From Aug to Dec 2019, a total of 37 patients were enrolled; most (94.6%) of the patients had ECOG PS of 1 and about half (48.6%) had received ≥3 prior systemic regimens. As of the data cut-off (22 May 2020), 28 patients remained on study treatment and 9 discontinued from pralsetinib (4 due to disease progression and 3 due to adverse events). The median treatment duration was 6.1 (range: 0.9-9.4) months. In 32 evaluable patients who had measurable disease at baseline per BICR, the ORR was 56.3% (95% CI: 37.7, 73.6) (1 complete response [CR] and 17 partial responses [PR]); in addition, 2 patients achieved PR pending confirmation. Clinical benefit rate (defined as the rate of confirmed CR or PR, or stable disease lasting ≥ 16 weeks from the first dose) was 81.3% (95% CI: 63.6, 92.8). Disease control rate was 96.9% (95% CI: 83.8, 99.9), and tumor regression was observed in all 13 patients with stable disease. The median time to response was 1.9 (range: 1.7-5.5) months. Median duration of response (DOR) was not reached; 6-month DOR rate was 83.1% (95% CI: 61.5, 100). All 37 patients experienced at least one treatment emergent adverse event (TEAE). The most frequently reported TEAEs were aspartate aminotransferase increased (83.8%), neutrophil count decreased (70.3%), anaemia (67.6%), white blood cell count decreased (56.8%), and hypertension (51.4%). Grade ≥ 3 TEAEs occurred in 25 (67.6%) patients, with the most common being neutrophil count decreased (24.3%), anaemia (24.3%), hypertension (16.2%), hypophosphataemia (13.5%), platelet count decreased (10.8%) and hypokalaemia (10.8%). There were no pralsetinib related AEs leading to death.

      Conclusion

      This is the first pivotal study to show that pralsetinib has deep and durable antitumor activity, and is well-tolerated in a cohort of Chinese patients with RET fusion+ NSCLC previously treated with platinum-based chemotherapy. The data are consistent with previously reported data from the global population in the ARROW trial. Overall, pralsetinib demonstrated a favorable benefit-risk profile, potentially offering a transformative medicine to Chinese RET-fusion driven advanced NSCLC patients.

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    IS06 - Industry Symposium Sponsored by Novartis: Novel Frontiers in the Treatment of NSCLC (ID 283)

    • Event: WCLC 2020
    • Type: Industry Symposium
    • Track:
    • Presentations: 3
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      IS06.01 - Welcome and Introduction (ID 4332)

      15:30 - 16:30  |  Presenting Author(s): Yi-long Wu

      • Abstract

      Abstract not provided

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      IS06.02 - Evolution of the NSCLC Treatment Landscape (ID 4333)

      15:30 - 16:30  |  Presenting Author(s): Yi-long Wu

      • Abstract

      Abstract not provided

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      IS06.07 - Closing (ID 4338)

      15:30 - 16:30  |  Presenting Author(s): Yi-long Wu

      • Abstract

      Abstract not provided

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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: 2
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      JICC01.01 - Chair (ID 4260)

      07:00 - 09:00  |  Presenting Author(s): Yi-long Wu

      • Abstract

      Abstract not provided

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      JICC01.14 - Efficacy and Safety of Pralsetinib in Chinese Patients with Advanced RET Fusion+ Non-Small Cell Lung Cancer after Platinum-Based Chemotherapy (ID 4273)

      07:00 - 09:00  |  Author(s): Yi-long Wu

      • Abstract

      Introduction
      RET fusions have been reported as oncogenic drivers in 1% to 2% of non-small cell lung cancer (NSCLC) patients. Pralsetinib is a highly potent and selective RET kinase inhibitor targeting oncogenic RET alterations. A global phase I/II ARROW study (NCT03037385) has demonstrated broad and durable antitumor activity of pralsetinib in a variety of advanced RET-altered solid tumors. Here we present the efficacy and safety results from the phase II NSCLC extension group that enrolled patients from China sites. Methods
      RET fusion+ Chinese NSCLC patients previously treated with platinum-based chemotherapy were enrolled and dosed with pralsetinib 400 mg QD. The primary objectives were to assess the objective response rate (ORR) by blinded independent central review (BICR) per RECIST v1.1 and safety profile in Chinese patients. Results

      From Aug to Dec 2019, a total of 37 patients were enrolled; most (94.6%) of the patients had ECOG PS of 1 and about half (48.6%) had received ≥3 prior systemic regimens. As of the data cut-off (22 May 2020), 28 patients remained on study treatment and 9 discontinued from pralsetinib (4 due to disease progression and 3 due to adverse events). The median treatment duration was 6.1 (range: 0.9-9.4) months. In 32 evaluable patients who had measurable disease at baseline per BICR, the ORR was 56.3% (95% CI: 37.7, 73.6) (1 complete response [CR] and 17 partial responses [PR]); in addition, 2 patients achieved PR pending confirmation. Clinical benefit rate (defined as the rate of confirmed CR or PR, or stable disease lasting ≥ 16 weeks from the first dose) was 81.3% (95% CI: 63.6, 92.8). Disease control rate was 96.9% (95% CI: 83.8, 99.9), and tumor regression was observed in all 13 patients with stable disease. The median time to response was 1.9 (range: 1.7-5.5) months. Median duration of response (DOR) was not reached; 6-month DOR rate was 83.1% (95% CI: 61.5, 100). All 37 patients experienced at least one treatment emergent adverse event (TEAE). The most frequently reported TEAEs were aspartate aminotransferase increased (83.8%), neutrophil count decreased (70.3%), anaemia (67.6%), white blood cell count decreased (56.8%), and hypertension (51.4%). Grade ≥ 3 TEAEs occurred in 25 (67.6%) patients, with the most common being neutrophil count decreased (24.3%), anaemia (24.3%), hypertension (16.2%), hypophosphataemia (13.5%), platelet count decreased (10.8%) and hypokalaemia (10.8%). There were no pralsetinib related AEs leading to death.

      Conclusion

      This is the first pivotal study to show that pralsetinib has deep and durable antitumor activity, and is well-tolerated in a cohort of Chinese patients with RET fusion+ NSCLC previously treated with platinum-based chemotherapy. The data are consistent with previously reported data from the global population in the ARROW trial. Overall, pralsetinib demonstrated a favorable benefit-risk profile, potentially offering a transformative medicine to Chinese RET-fusion driven advanced NSCLC patients.

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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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      MA01.10 - MDM2 Inhibitor APG-115 Suppresses Cell Proliferation and Tumor Growth in Preclinical Models Of NSCLC Harboring STK11 Mutations (ID 1438)

      11:45 - 12:45  |  Author(s): Yi-long Wu

      • Abstract

      Introduction

      Liver kinase B1 (LKB1/STK11) is one of the most frequent mutated genes in non-small-cell lung cancer (NSCLC). Patients harboring STK11 mutations proven resistant to immunotherapy and lacking of effective therapies. A published genomic database indicates MDM2 inhibition is effective in NSCLC cells carrying STK11 mutations. Currently in clinical development, APG-115 is a novel, orally active small-molecule mouse double minute 2 homolog (MDM2) inhibitor. APG-115 potently activates P53 pathway and induces apoptosis in TP53 wild-type tumors.

      Methods

      We first investigated the effect of APG-115 on cell proliferation in a panel of human TP53 wild-type NSCLC cell lines with (i.e., A549, H460, H1944, H1666) or without (i.e., H226, H292) STK11 mutations. Next, a panel of 10 TP53 wild-type patient-derived xenograft (PDX) models of NSCLC with or without STK11 mutations were used to validate in vitroresults. Lastly, we investigated the involvement of ferroptosis to explore the mechanisms of action of APG-115.

      Results

      APG-115 more effectively inhibited cell growth in STK11-mutant cell lines in vitro, giving rise to the half maximal inhibitory concentration (IC50) values ranging from 0.15 to 0.38 μM in comparison with 0.18 to 1.8 μM in wild-type cell lines. In vivo, oral administration of APG-115 (100 mg/kg) daily for 14 days led to substantial tumor growth inhibition in 3 out of 10 PDX models (30%). Among these 3 models, two harbored STK11 mutations. Furthermore, the response rate in PDXs harboring mutant STK11 is higher than the wildtype group (66% vs 14%).The above results indicate that STK11mutations may further enrich the responders to APG-115 therapy. Considering that the disorder in AMP-activated protein kinase (AMPK) pathway sensitizes cancer cells to ferroptosis-mediated cell deaths, we further unveiled that, in comparison with the wild-type cell lines, STK11-mutant cell lines showed significantly increased lipid peroxidation level after APG-115 intervention, suggesting that the effect of APG-115 is mediated by ferroptosis.

      figure abcd.jpg

      Conclusion

      APG-115 is more effective in inhibiting cell proliferation and tumor growth in STK11-mutant NSCLC cells and xenograft models, respectively, in comparison with the wild-type counterparts. Further, antitumor activity of APG-115 in STK11-mutant tumors may be mediated through ferroptosis. Taken together, our data warrant clinical investigation of APG-115 in treating NSCLC tumors with STK11 mutations.

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    MA02 - Technological Advances in Diagnostics, Imaging and Therapeutics for Lung Cancer (ID 103)

    • Event: WCLC 2020
    • Type: Mini Oral
    • Track: Diagnostics and Interventional Pulmonology
    • Presentations: 1
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      MA02.08 - Computed Tomography Attenuation Value as Considerable Predictor for Malignancy in Clinical T1 Lung Adenocarcinoma (ID 1611)

      14:15 - 15:15  |  Author(s): Yi-long Wu

      • Abstract

      Introduction

      To explore the quantitative variables of thoracic computed tomography for predicting the pathologic malignancy of cT1 lung adenocarcinoma.

      Methods

      We retrospectively collected data from 96 consecutive patients with clinical T1 lung adenocarcinoma. -160 Hu was used as the cutoff of solid and ground glass opacity portion. AAH, AIS, MIA and LPA were considered as less malignant (LM), while other subtypes of IACs were included into more malignant (MM) group.

      Results

      The area under receiver operating characteristic curves of m-CT value, D_solid, D_whole, Area_solid, Area_whole, 1D_CTR and 2D_CTR were respectively 0.89 (95%CI, 0.81 ~ 0.97; Se=83%, Sp=93%), 0.895 (95%CI, 0.832 ~ 0.958; Se=88%, Sp=79%), 0.736 (95%CI, 0.634 ~ 0.839; Se=87%, Sp=60%), 0.89(95%CI, 0.82 ~ 0.96; Se=87%, Sp=81%), 0.738 (95%CI, 0.634 ~ 0.841; Se=83%, Sp=63%), 0.861 (95%CI, 0.780 ~ 0.942; Se=90%, Sp=74%), 0.869 (95%CI, 0.788 ~ 0.949; Se=85%, Sp=84%). Multiple logistic regression revealed that mean CT value was the independent risk predictor of more pathologically malignancy of clinically T1 lung adenocarcinoma (p=0.003).

      Table1: Clinicopathological comparison between the less malignant and more malignant groups
        Less malignant(n=43) More malignant(n=53) p value
      Age, years, mean 56.12 65.38 <0.001
      Gender     >0.05
      Male 13 22  
      Female 30 31  
      Loaction     >0.05
      RUL 21 19  
      RML 3 3  
      RLL 7 12  
      LUL 7 10  
      LLL 5 9  
      D_solid(mm) 2.18 13.32 <0.001
      D_whole(mm) 16.84 23.13 <0.001
      Area_solid(mm²) 8.73 122.32 <0.001
      Area_whole(mm²) 187.44 322.56 <0.001
      1D_CTR 0.13 0.56 <0.001
      2D_CTR 0.07 0.35 <0.001
      2D m-CT Value(Hu) -629.40 -348.55 <0.001
      EGFR Mutation     >0.05
      Mutation 19 25  
      Wild type 18 25  
      ALK Mutation     >0.05
      Mutation 0 2  
      Wild type 30 43  
      D_solid: the longest diameter of the solid portion in the greatest horizontal section of nodule; D_whole: the longest diameter of the greatest horizontal section of nodule; Area_solid: the area of the solid portion in the greatest horizontal section of nodule; Area_whole: the area of the greatest horizontal section of nodule; 1D_CTR: D_solid/D_whole; 2D_CTR: Area_solid/Area_whole; m-CT value: mean CT attenuation value of the greatest horizontal section of nodule. mm: millimeter; CTR: consolidation tumor ratio. Hu: Hounsfield unit.
      Table2: Univariate and multivariate analysis for predicting the more pathologically malignant cT1 lung adenocarcinoma.
          Univariate analyses Multivariate analyses
        Category odd ratio 95% CI p value odd ratio 95% CI p value
      Age continuity 1.075 1.032~1.119 <0.001 1.019 0.955~1.088 0.56
      Gender Male vs Female 0.611 0.261~1.428 0.255      
      D_solid(mm) ≤3.473 vs > 3.473 29.593 9.624~90.996 <0.001 6.086 0.079~469.082 0.415
      D_whole(mm) ≤14.807 vs >14.807 10.05 3.686~27.402 <0.001 14.991 0.635~353.753 0.093
      Area_solid(mm²) ≤6.513 vs >6.513 28.75 9.517~86.850 <0.001 0.258 0.10~6.642 0.413
      Area_whole(mm²) ≤156.641 vs >156.641 8.25 3.201~21.265 <0.001 0.336 0.017~6.748 0.476
      1D_CTR ≤0.124 vs >0.124 27.927 8.862~88.011 <0.001 0.546 0.015~19.903 0.741
      2D_CTR ≤0.040 vs >0.040 25.143 8.526~74.148 <0.001 4.232 0.454~39.442 0.205
      m-CT Value(Hu) ≤-494.927 vs >494.927 65.185 16.481~257.815 <0.001 19.723 2.783~139.780 0.003
      95%CI: 95% confidential index; mm: millimeter; CTR: consolidation tumor ratio. Hu: Hounsfield unit.

      figue.jpg

      Conclusion

      Mean CT attenuation value is useful for predicting the higher pathologically malignant degree of clinical T1 lung adenocarcinoma. M-CT value is a potential reference factor for the formulation of surgical procedure for cT1 lung adenocarcinoma.

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    MA04 - Health Policy and the Real World (ID 217)

    • Event: WCLC 2020
    • Type: Mini Oral
    • Track: Health Services Research/Health Economics
    • Presentations: 1
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      MA04.06 - Clinical Characteristics and Outcomes in Advanced KRAS Mutant NSCLC – A Multi-Centre Collaboration in Asia (ATORG-005) (ID 3475)

      16:45 - 17:45  |  Author(s): Yi-long Wu

      • Abstract

      Introduction

      KRAS driver mutations in advanced NSCLC have long been considered to be undruggable. However, promising efficacy data from early phase trials of novel therapies targeting KRAS have renewed focus on KRAS as an oncogenic driver. There is limited data on the prognostic and predictive significance of KRAS mutation subtypes. We present an interim analysis of a real world observational multi-centre study of advanced KRAS mutant NSCLC patients from five countries in Asia, conducted by the Asian Thoracic Oncology Research Group (ATORG).

      Methods

      Patients with advanced KRAS mutant NSCLC treated with at least one line of systemic therapy at tertiary centres in five Asian countries (China, India, Japan, Singapore, South Korea) between Jan 2014 and Dec 2018 were included. Baseline clinical characteristics, molecular profile and treatment outcomes were collected (median follow-up 35.5 months, 95%CI 28.7-50.3).

      Results

      A total of 155 patients were included in this interim analysis, with median age at advanced stage diagnosis 63 years (interquartile range [IQR] 56-70), 93% were ECOG 0-1, 70% were male and 64% were current or ex-smokers. In terms of ethnicity, 39% were Korean, 36% were Chinese, 15% were Japanese, 8% were Indian and 2% were Malay. Baseline histology was adenocarcinoma in 90%, squamous cell carcinoma in 4% and other histologies in 6%. KRAS mutation was detected by NGS in 141 (91%) patients, Sanger sequencing in 12 (8%) patients and RT-PCR in 2 (1%) patients. KRAS G12C (26%) was most common, followed by G12D (23%) and G12V (21%). The incidence of KRAS G12C mutation in patients with a smoking history was 35/99 (35%) compared with 6/56 (11%) in patients without any smoking history. Co-alterations were found with EGFR mutations (14%), ALK fusions (1%), ROS1 fusions (1%) and BRAF mutations (3%). PD-L1 TPS was 0% in 22%, 1-49% in 19%, ≥50% in 14% and unknown/not tested in 45%. Brain metastases were present at advanced stage diagnosis in 25% and lifetime prevalence was 35%. Patients received a median 2 lines of therapy. First-line systemic therapy consisted of chemotherapy alone (66%), targeted therapy (15%) or other therapies (19%). Median time to next treatment (TTNT) on first-line chemotherapy alone was 7.3 months (95%CI 5.0-9.5). Overall, the median TTNT for first-line and second-line therapy was 7.7 (95%CI 6.5–10.0) and 7.0 (95%CI 5.3–10.9) months, respectively. 63% of patients had died, and 37% of patients were still alive or lost to follow-up at the time of data cut-off. Median OS for the overall cohort was 21.6 months (95%CI 15.9-27.6). Median OS was greater in immunotherapy treated (alone or in combination at any line; 45%) versus non-immunotherapy treated (55%) patients (27.6 [95%CI 19.1-37.9] months versus 15.4 [95%CI 10.3-23.7] months, HR 1.8, 95%CI 1.2-2.7, logrank p=0.005).

      Conclusion

      In Asian KRAS mutant NSCLC, duration of first-line therapy and survival outcomes remain poor – emphasising the need for greater therapeutic options for patients with a KRAS driver mutation. Additional sites/countries are planned and recruitment to this study is ongoing.

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    OA06 - Updates on EGFR Targeted Perioperative Therapy and Precision Adjuvant Chemotherapy (ID 118)

    • Event: WCLC 2020
    • Type: Oral
    • Track: Early Stage/Localized Disease
    • Presentations: 2
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      OA06.03 - Patient-Reported Outcomes from ADAURA: Osimertinib as Adjuvant Therapy in Patients with Resected EGFR Mutated (EGFRm) NSCLC (ID 3505)

      16:45 - 17:45  |  Author(s): Yi-long Wu

      • Abstract

      The abstract for this presentation is currently under embargo or has not been submitted.

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      OA06.04 - Postoperative Chemotherapy Use and Outcomes from ADAURA: Osimertinib as Adjuvant Therapy for Resected EGFR Mutated NSCLC (ID 3464)

      16:45 - 17:45  |  Presenting Author(s): Yi-long Wu

      • Abstract

      The abstract for this presentation is currently under embargo or has not been submitted.

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    P59 - Tumor Biology and Systems Biology - Basic and Translational Science - Genomics (ID 197)

    • 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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      P59.03 - Intratumoral Heterogeneity and Clonal Evolution in Large Non-Small Cell Lung Cancer (>7cm) Delineated by Multiregion Sequencing (ID 1305)

      00:00 - 00:00  |  Author(s): Yi-long Wu

      • Abstract
      • Slides

      Introduction

      T4N0M0 (size > 7cm) non-small cell lung cancer (NSCLC) represent relatively favorable prognosis in stage IIIA category, probably due to the limited metastatic potential. The intratumor genomic profile of these oversize tumors have not been well studied.

      Methods

      T4N0M0 surgical NSCLC patients were enrolled. Whole-exome sequencing on three regions of each surgical tumor was performed. Single nucleotide variation (SNV), small insertion and deletions (Indels), and copy number variation were called and used for the analysis of intratumoral heterogeneity (ITH). Driver genes were identified by a gene list from the research of Matthew H. Bailey 2018. Tumor mutation burden (TMB) was calculated using all somatic nonsynonymous mutations (variant allele frequency > 0.03). Phylogenetic trees were constructed by regionally shared and private alterations.

      Results

      Five NSCLC were enrolled, including three adenocarcinoma and two squamous cell carcinoma. 15 tumor regions were sequenced successfully, with a median coverage of 452×. Interestingly, two distant ITH/TMB phenotypes were found, ITHlow/TMBhi (P1,P4,P5) andITHhi/TMBlow (P2,P3). The average heterogeneous somatic mutations in these two categories were 36% vs 98%, while the TMB was 154 vs 19. The ITHlow/TMBhi type had higher proportion of trunk SNV and Indels (62.2%, 53.2, and 65.5%, respectively), while ITHhi/TMBlow had lower of trunk (0% and 3.2%). In total, 11 driver mutations were identified and 72.73% of the driver mutations located on the trunks of tumor phylogenetic trees, including KEAP1, TP53, FAT1, CDKN2A, SMARCA4, and FAT1.

      Conclusion

      Our data implied two distant ITH/TMB phenotypes in the T4N0M0 NSCLC (>7cm). It may contribute to our need for further understanding of tumor indolent growth pattern.

      fig 1.jpg

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    P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 3
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P76.60 - FLAIR: Phase II Study of Osimertinib plus Bevacizumab versus Osimertinib in Advanced NSCLC Patients with EGFR L858R Mutation (ID 3221)

      00:00 - 00:00  |  Author(s): Yi-long Wu

      • Abstract
      • Slides

      Introduction

      The 3rd generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), osimertinib monotherapy has been considered as the new standard of care for advanced EGFR mutated non-small-cell lung cancer (NSCLC) patients. However patients with L858R mutation have achieved lower efficacy of EGFR-TKIs than those with 19Del mutation, even with osimertinib. Herein to improve the efficacy of L858R population is still unmet medical needs. While CTONG1509 study has presented the addition of bevacizumab to 1st generation EGFR TKI erlotinib appears to significantly improve L858R patients’ progression free survival the combination of osimertinib and bevacizumab is worth deep exploration.

      Here we present the rationale and study design for the FLAIR trial, a multicenter, open label, randomized, phase II study.

      Methods

      Study entry will be limited to adults aged ≥ 18 years with primary recurrent or metastatic nonsquamous non-small-cell lung cancer with documented an EGFR exon 21 L858R mutation. Patients will be randomized 1:1 to receive osimertinib 80 mg once daily plus bevacizumab 15mg/kg every 3 weeks or osimertinib monotherapy 80 mg once daily until disease progression or unacceptable toxicity.

      The primary endpoint is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR), duration of overall response (DoR), time to treatment failure (TTF), overall survival rate at 2 years, and safety and tolerability.

      In the HR assumption of 0.65, sample size of 90 patients is driven by the needs of 67% statistic power for the test at the significance level of 0.2, two sided, with the accrual period of 8 months and the longest follow-up of 32 months.

      The first analysis (primary analysis) data cut-off (DCO) point will be happened when 70% data maturity for PFS based on investigator assessment (according to RECIST 1.1) has been reached (depending on the actual event rate).

      o+t.jpg

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      P76.67 - Safety and Efficacy of First-Line Dacomitinib in Advanced Non-Small Cell Lung Cancer by EGFR Mutation SUBtype in ARCHER 1050 (ID 3335)

      00:00 - 00:00  |  Author(s): Yi-long Wu

      • Abstract
      • Slides

      Introduction

      ARCHER 1050 (NCT01774721) compared dacomitinib versus gefitinib in newly diagnosed patients with advanced EGFR-mutation positive non-small cell lung cancer (NSCLC). Updated overall survival (OS) analysis showed significant improvement in OS with dacomitinib versus gefitinib in the overall population and exon 21 L858R substitution mutation (L858R) subgroup. We report analysis of efficacy and safety by EGFR mutation subtype.

      Methods

      In this ongoing, open-label, phase III trial, eligible patients were randomized 1:1 to dacomitinib 45 mg/day (n = 227) or gefitinib 250 mg/day (n = 225), stratified by race and EGFR mutation subtype (exon 19 deletion [Del19] or L858R). The primary endpoint was PFS (blinded independent radiologic central review). Post-hoc exploratory efficacy analyses for patients with dacomitinib dose reductions were also conducted.

      Results

      Improvements in PFS and updated OS with dacomitinib over gefitinib were observed in patients with dacomitinib dose reduction in both EGFR mutation subgroups (Table 1). In responding patients, duration of response was longer with dacomitinib versus gefitinib in both EGFR mutation subgroups. Dacomitinib dose reduction was reported in 66% (Del19) and 67% (L858R) of patients for PFS (data cutoff date July 29, 2016) and 68% (Del19 and L858R) of patients for updated OS (data cutoff date May 13, 2019; extended median follow-up 47.9 months). Median duration of treatment with dacomitinib was 16.5 months (range 0.2-35.0) and 13.2 months (range 0.1-37.4) in the Del19 and L858R subgroups, respectively. Safety data are in Table 2.

      table 1.png105176 wclc 2020 daco archer mut sbgrp abs_table 2_updated 08 sep 2020.png

      Conclusion

      Dacomitinib is the first second-generation TKI to improve PFS and OS over gefitinib in patients with dose reduction in both Del19 and L858R subgroups. The difference in treatment durations of the dacomitinib subgroups may affect frequency of Grade ≥3 TEAEs. Potential differences in safety between EGFR mutation subgroups will warrant further exploration.

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      P76.78 - Evaluation of the Development of Brain Metastases in Patients Treated with Dacomitinib or Gefitinib from ARCHER 1050 Study (ID 3461)

      00:00 - 00:00  |  Author(s): Yi-long Wu

      • Abstract
      • Slides

      Introduction

      Dacomitinib (Vizimpro®) is a competitive, irreversible, small-molecule inhibitor of epidermal growth factor receptor (EGFR). ARCHER 1050 is a multicenter, Phase 3 study conducted in patients with metastatic or recurrent NSCLC harboring EGFR activating mutations (exon 19 deletion or exon 21 L858R substitution mutations) with no prior therapy for metastatic disease. Dacomitinib significantly improved progression-free survival (PFS) and overall survival (OS) against gefitinib with hazard ratios of 0.59 (p<0.001) and 0.75 (p=0.0155), respectively. The present analysis evaluated the risk factors of development of brain metastases from ARCHER 1050, including treatment, baseline characteristics, and dacomitinib exposure.

      Methods

      CNS imaging was performed in ARCHER 1050 at baseline for all patients and on treatment for patients with clinically suspected brain metastases at the discretion of investigators. Brain lesion data were recorded based on investigator (INV) and independent radiologic central (IRC) reviews. Patients, excluding any history or evidence of brain or leptomeningeal metastases as per the protocol exclusion criteria, were randomized to receive dacomitinib (starting dose of 45 mg QD with allowance of dose reduction to 30 mg or 15 mg) or gefitinib (250 mg QD). Dacomitinib exposure was measured by population PK model-based trough concentrations, average concentrations, or AUC at the end of Cycle 1. Other baseline characteristics were evaluated for its potential association with on treatment development of brain metastases using logistic regression (glm() function).

      Results

      Based on INV review, no patients in the dacomitinib arm (n=227) presented with baseline brain metastases and 1 patient presented with baseline brain metastases in the gefitinib arm (n=225). After median follow up of 22.1 months, total of 4 (1.8%) patients developed brain metastases in the dacomitinib arm comparing to 14 (6.2%) in the gefitinib arm [odds ratio (OR): 0.27 (95% CI: 0.08, 0.77; p=0.0229)]. Of the 4 patients with developed brain metastases in the dacomitinib arm, 1 patient had no dose reduction and the other 3 patients had dose reduced to 30 mg QD. Similarly, by IRC review, no patients presented with brain metastases at baseline in dacomitinib arm while 4 patients in gefitinib arm were retrospectively found to have baseline brain metastases. According to IRC, only 1 (0.4%) patient in dacomitinib arm and 9 (4.0%) patients in gefitinib arm developed new brain lesions [OR: 0.11 (95% CI: 0.01, 0.57; p=0.0341)]. No other covariates (eg., smoking status, race, sex, baseline ECOG performance status, EGFR mutation type, and baseline brain metastases) were associated with development of new brain lesions. Dacomitinib exposure was explored as a covariate for the INV reported new brain lesions and was not found to be associated with development of brain metastases.

      Conclusion

      Dacomitinib is associated with a lower incidence of symptomatic CNS progression in the ARCHER 1050 study.

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    P85 - Targeted Therapy - Clinically Focused - MET (ID 262)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P85.02 - NGS could not Replace FISH Regarding to MET Amplification as an Optimal Biomarker (ID 1581)

      00:00 - 00:00  |  Author(s): Yi-long Wu

      • Abstract
      • Slides

      Introduction

      MET amplification (MET amp) is known as an important mechanism of resistance to EGFR-TKIs in NSCLC. We investigated the association between survival benefits and MET status identified by different methods, to explore the appropriate biomarker to select patient for MET-TKIs treatment in advanced NSCLC.

      Methods

      Method: FISH (fluorescence in situ hybridization), IHC (immunohistochemistry) and NGS (next generation sequences) were performed prospectively from FFPE/liquid samples with NSCLC. MET amplification by FISH was defined as MET/CEP7 ratio>2 or CN(copy number )>6 and served as the standard reference for over-express by IHC and copy number gain (CNG) by NGS. Objective response (OR) and PFS were used to confirm optimal biomarker for MET inhibitor.

      Results

      We identified MET dysregulation of 37 NSCLC patients by FISH, IHC and NGS before MET-TKIs administration and assessing the survival benefits of 33 cases treated MET inhibitor. The consistence of FISH, IHC and NGS was only 54%. They are the different population. MET amplification identified by FISH proved the best predictive efficiency for survival benefits. The PR rate was 82% (18/22) and median PFS was 4.8 months in MET amp, compared to 1.0 months for cases with non-MET amp (P= 0.004). Both MET dysregulations identified by NGS or IHC failed to distinguish the significant survival difference in patients with MET-TKIs. Comparing with MET amplification by FISH, effective cases were more seen in patients with CNG > 4.0 or IHC score >290 . Based on these two cut-off values:CNG > 4.0 or IHC score >290 still did not predict efficacy of MET inhibitors, suggesting CNG by NGS had no significant associations with efficacy benefits.

      Conclusion

      Compared to MET amplification identified by FISH, CNG dysregulation by NGS or MET protein over-express by IHC could not serves as the predictive biomarker for MET inhibitors.

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    PL01 - Opening Plenary Session (Japanese, Mandarin, Spanish Translation Available) (ID 140)

    • Event: WCLC 2020
    • Type: Plenary
    • Track: N.A.
    • Presentations: 1
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      PL01.01 - Chair (ID 3894)

      18:00 - 20:00  |  Presenting Author(s): Yi-long Wu

      • Abstract

      Abstract not provided

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    PL05 - Affordable and Accessible Lung Cancer Care (Japanese, Mandarin, Spanish Translation Available) (ID 146)

    • Event: WCLC 2020
    • Type: Plenary
    • Track: N.A.
    • Presentations: 1
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      PL05.01 - Chair (ID 3926)

      18:00 - 20:00  |  Presenting Author(s): Yi-long Wu

      • Abstract

      Abstract not provided