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You Lu



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    JCSE01 - Joint IASLC-CSCO-CAALC Session (ID 63)

    • Event: WCLC 2019
    • Type: Joint IASLC-CSCO-CAALC Session
    • Track:
    • Presentations: 1
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      JCSE01.28 - Changes of Brain Structure in Advanced NSCLC Patients Receiving EGFR-TKIs: Dynamic Analysis Based on Series MRI Images (ID 3865)

      07:00 - 11:15  |  Author(s): You Lu

      • Abstract
      • Slides

      Abstract
      Background
      EGFR-TKI was the standard care for metastatic NSCLC patients harboring positive EGFR mutation, which might inhibit EGF signaling pathway and consequently have effect on differentiation, maturation and rehabilitation of neural cells. For the first time, we evaluated the dynamic changes of white matter lesion (WML) and gray matter volume (GMV) among such patients based on series of MRI images.

      Methods
      We retrospectively identified 778 patients with pathologically diagnosed advanced NSCLC receiving first-generation EGFR-TKIs in our hospital from 2010 to 2017, and 75 patients without brain metastasis and else comorbidity (hypertension, etc.) were analyzed. The modified Scheltens visual scale were performed to evaluate the changes of WML based on the series (baseline, 12 months' point and 24 months' point) of MRI images, and CBM (cluster-based morphometry) method based on SPM12 were adopted to identify GMV loss. The statistical methods were performed using SPSS software 22.0.

      Results
      During the 24-month EGFR-TKI treatment, the patient's WML visual scores showed a progressive worsen. Comparing to the baseline (6.680±3.636), the scores were significantly changed at the 12 months' point (8.650±3.857; Mean scores increasing 1.973, 95% CI 1.595-2.352, p<0.001) and changed more obviously at the 24 months' point (10.110±3.854; Mean scores increasing 3.427, 95% CI 2.979-3.874, p<0.001), respectively. Also, the significant GMV loss were found in subregions of the right occipital lobe (mean decrease 76.714, 95% CI 40.739-112.690), left occipital lobe (mean decrease 93.476, 95% CI 37.483-149.469) and left basal ganglia (mean decrease 37.571, 95% CI 21.576-53.567), respectively (all p<0.005, the cluster level FDR<0.05).

      Conclusion
      Dynamic structural analysis of series brain MRI images showed the significant worsen of the WML and GMV loss in patients with advanced NSCLC receiving EGFR-TKIs chronically. Perspective studies are warranted to verify its impact on the cognitive deficiency and hypomnesis among these patients in future.

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    OA02 - A New Vision of Targets and Strategies (ID 120)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
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      OA02.03 - The Third Generation EGFR Inhibitor (EGFR-TKI) HS-10296 in Advanced NSCLC Patients with Resistance to First Generation EGFR-TKI (Now Available) (ID 766)

      10:30 - 12:00  |  Author(s): You Lu

      • Abstract
      • Presentation
      • Slides

      Background

      HS-10296 is an oral, potent, high selective third generation EGFR tyrosine-kinase inhibitor (EGFR-TKI) for sensitizing mutations, and the EGFR Thr790Met (T790M) resistance mutation which has been demonstrated by phase I study. This phase II, open-label, multicenter single-arm study was designed to confirm the efficacy and safety of HS-10296 in a large population of non-small-cell lung cancer (NSCLC) patients with EGFR T790M mutation, who had progressed after first generation EGFR-TKI treatment.

      Method

      Patients aged at least 18 years with centrally confirmed EGFR T790M-positive mutations, locally advanced or metastatic (stage IIIB/IV) NSCLC after first generation EGFR-TKI treatment received HS-10296 110 mg orally once daily until disease progression, or intolerable toxicity, or patient withdrawal. Patients with asymptomatic, stable brain metastases not requiring steroids were allowed to enroll. The primary endpoint was the objective response rate (ORR) by independent central review using Response Evaluation Criteria in Solid Tumors, version 1.1 every 6 weeks. Response endpoints (ORR and disease control rate [DCR]) were assessed in response analysis set. Secondary end points including progression-free survival (PFS), duration of response (DoR), depth of response (DepOR), overall survival (OS) and safety were evaluated in full analysis set. The final data cutoff was on Jan 5, 2019. The study is still ongoing.

      Result

      Totally, 244 patients (median age 60.8) entered study in 36 sites in mainland China (189 patients) and Taiwan (55 patients) between May 16, 2018 to Oct 23, 2018. 2 patients were excluded from the evaluable for response analysis set (n=242) due to absence of measurable disease at baseline by independent central review. At data cutoff, 182 (74.6%) patients remained on treatment. The median duration of follow-up was 4.7 months. 160 of 242 patients achieved confirmed partial responses by independent central review. The ORR was 66.1% (95% CI: 59.8-72.1). The DCR was 93.4% (95% CI: 89.5-96.2). The most common adverse reactions (≥ 10%) were blood creatine phosphokinase increased (43 [17.6%]), aspartate aminotransferase increased (29 [11.9%]), pruritus (28 [11.5%]), rash (28 [11.5%]) and alanine aminotransferase increased (26 [10.7%]). The most common all-causality grade 3 and 4 adverse events were blood creatine phosphokinase increased (14 [5.7%]) and hyponatraemia (4 [1.6%]). Serious adverse events were reported in 30 (12.3%) patients, of which 19 (7.8%) were investigator assessed as possibly treatment-related to HS-10296. Three deaths were due to adverse events; one was related to cardiopulmonary failure, other two events occurred after disease progression. There was no interstitial lung disease during study treatment.

      Conclusion

      HS-10296 has demonstrated good clinical benefit with minimal toxicity in patients with EGFR T790M-positive NSCLC patients who have progressed after first generation EGFR-TKI treatment. The Phase III study has already launched comparing HS-10296 with gefinitib in advanced NSCLC patients with EGFR sensitizing mutations. (The study was sponsored by Jiangsu Hansoh Pharmaceutical Co., Ltd.; ClinicalTrials.gov number, NCT02981108)

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    OA11 - Decomplexifying Molecular Targets, Immunotherapy and Treatment Settings in the Real World (ID 137)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Now Available
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      OA11.02 - Changes of Brain Structure in Advanced NSCLC Patients Receiving EGFR-TKIs: Dynamic Analysis Based on Series MRI Images (Now Available) (ID 314)

      14:00 - 15:30  |  Author(s): You Lu

      • Abstract
      • Presentation
      • Slides

      Background

      EGFR-TKI was the standard care for metastatic NSCLC patients harboring positive EGFR mutation, which might inhibit EGF signaling pathway and consequently have effect on differentiation, maturation and rehabilitation of neural cells. For the first time, we evaluated the dynamic changes of white matter lesion (WML) and gray matter volume (GMV) among such patients based on series of MRI images.

      Method

      We retrospectively identified 778 patients with pathologically diagnosed advanced NSCLC receiving first-generation EGFR-TKIs in our hospital from 2010 to 2017, and 75 patients without brain metastasis and else comorbidity (hypertension, etc.) were analyzed. The modified Scheltens visual scale were performed to evaluate the changes of WML based on the series (baseline, 12 months' point and 24 months' point) of MRI images, and CBM (cluster-based morphometry) method based on SPM12 were adopted to identify GMV loss. The statistical methods were performed using SPSS software 22.0.

      Result

      During the 24-month EGFR-TKI treatment, the patient's WML visual scores showed a progressive worsen. Comparing to the baseline (6.683.636), the scores were significantly changed at the 12 months' point (8.650±3.857; Mean scores increasing 1.973, 95% CI 1.595-2.352, p<0.001) and changed more obviously at the 24 months' point (10.113.854; Mean scores increasing 3.427, 95% CI 2.979-3.874, p<0.001), respectively. Also, the significant GMV loss were found in subregions of the right occipital lobe (mean decrease 76.714, 95% CI 40.739-112.690), left occipital lobe (mean decrease 93.476, 95% CI 37.483-149.469) and left basal ganglia (mean decrease 37.571, 95% CI 21.576-53.567), respectively (all p<0.005, the cluster level FDR<0.05).

      Conclusion

      Dynamic structural analysis of series brain MRI images showed the significant worsen of the WML and GMV loss in patients with advanced NSCLC receiving EGFR-TKIs chronically. Perspective studies are warranted to verify its impact on the cognitive deficiency and hypomnesis among these patients in future.

      2019322fig1.jpg

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.