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Xiaodong Zhang



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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): Xiaodong Zhang

      • Abstract
      • Slides

      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): Xiaodong Zhang

      • 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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    P38 - Pathology - Pathology/Staging (ID 108)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P38.06 - Evaluation of Non-invasive Transcutaneous Bioconductance Measurement - a Risk-Stratification Biomarker for Suspicious Pulmonary Lesions (ID 2263)

      00:00 - 00:00  |  Author(s): Xiaodong Zhang

      • Abstract
      • Slides

      Introduction

      By conducting low dose CT screening program in the high-risk population, a large number of pulmonary nodules have been discovered by the radiology image. There is an urgent need for risk stratification biomarkers for pre-interventional assessment of growing numbers of Indeterminate Pulmonary Lesions (IPL). In the previous study, we found the bioconductance through normal lung parenchyma differs from pathologic lesions, including inflammation and malignant tumors. Using non-invasive multi-point and multiparametric measurements of transcutaneous bioconductance, the previous single-center open-labeled feasibility trial (JTO 2012;7:681) developed an algorithm with high-performance AUC/accuracy 90%. Subsequent prospective multi-center trials in US (NCT01566682) and China had lower performances (60% accuracy) attributed to data overfitting and inconsistent human performances. In this abstract, we presented the latest multi-center prospective trial (NCT0156668; China reg20170226) evaluating revised Prolung test protocol.

      Methods

      Institutions IRB approved the recruitment of subjects undergoing multidisciplinary evaluation of IPLs, undergo single Prolung Test measurement before biopsies. Protocol modified from previous studies; briefly only 20 surface points interrogated instead of 62, 3X measurement plus within-patient calibration improved measurement consistency. Operator training and criteria for subjects’ enrollment also modified. Collected bioconductance data is analyzed on a modified algorithm, and binary malignancy prediction score (increased/decreased) generated and locked prior to follow-up interventions. In this non-interventional study, the result of prediction is withheld from clinical investigators prior to the final diagnosis.

      Results

      418 of 486(86%) enrolled subjects evaluable for the outcome. Demographic distribution: male:female 44%/56%. Age range 3rd-9th decades with significant clustering around the 5th-6th decades (64%). Tissue diagnostic modalities are by surgery (193=46%) and bronchoscopy (84=20%), non-diagnostic biopsies followed by radiology(141=34%). Based on the pathological diagnosis, it includes 221(52.9%) cancers and 197(47.1%) benign. Cancer cell type predominantly adenocarcinoma (84.7%), squamous ca (9.1%), other cell types (6.2%). Test performance (Figure 1) demonstrates Sensitivity 84.2%, Specificity 73.6%, overall accuracy 79.2%, PPV 78.2%, NPV 80.6%. Focusing on the 153/193(79.3%) surgical group with pathologic staging, 128 stage I patients had a test sensitivity of 83.6%. Accuracy of test stable across size ranges 82%(4-8mm), 77.2%(8-30mm), 80%(30-50mm).

      figure 1.png

      Conclusion

      In this blinded prospective validation trial, the current iteration of the Prolung Test(v2.0) has significantly improved sensitivity (84.2% vs 70-75%) and specificity (73.6% vs 47-50%) over the previous version, based on the streamlined protocol of human operations and minor algorithm development. Overall performance achieved without subgroup selection based on risk score and without degradation in smaller stage I cancers. Efficacy as a follow-up tool and further benefits from hardware modifications await studies.

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

    • 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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      P76.65 - CNS Efficacy of AST2818 in Patients with T790M-Positive Advanced NSCLC: Data from a Phase I-II Dose-Expansion Study (ID 3286)

      00:00 - 00:00  |  Author(s): Xiaodong Zhang

      • Abstract
      • Slides

      Introduction

      Furmonertinib (AST2818, former name: alflutinib) is a new third-generation EGFR-tyrosine kinase inhibitor that selectively inhibits EGFR-sensitizing and EGFR T790M mutation. We have reported promising clinical activity and well-characterized tolerability of AST2818 in EGFR T790M-positive locally advanced or metastatic non-small-cell lung cancer (NSCLC) patients including its preliminary efficacy in patients with central nervous system (CNS) metastases (Shi Y et al JTO 2020;15(6):1015-1026). Herein, we report the result of recent subgroup analysis from phase I-II dose-expansion study (NCT03127449) where the CNS efficacy of different AST2818 doses was evaluated.

      Methods

      Patients aged ≥18 years with centrally confirmed EGFR T790M-positive locally advanced or metastatic NSCLC received AST2818 ranging from 40-240 mg doses once daily until disease progression. Patients with asymptomatic, stable CNS metastases not requiring steroids for at least 4 weeks before the first dose of AST2818 were enrolled. A subgroup analysis was conducted in patients with ≥1 measurable CNS lesion (per RECIST 1.1) at baseline brain imaging (CNS evaluable-for-response set, cEFR) and patients with ≥1 measurable and/or non-measurable CNS lesion at baseline brain imaging (CNS full analysis set, cFAS) by blinded independent central review (BICR). CNS efficacy was evaluated in terms of CNS objective response rate (ORR), CNS disease control rate (DCR), CNS progression-free survival (PFS), and CNS duration of response (DoR) (assessed by BICR).

      Results

      At data cutoff (29 January 2020), 116 patients were enrolled, of which 45 patients (38.8%) were included in cFAS and 23 patients (19.8%) were included in cEFR. Confirmed CNS ORR was 65.2% (15/23) while CNS DCR was 91.3% (21/23) in cEFR. The CNS ORR in the 40-, 80-, 160-, and 240-mg groups was 0 (no response of 1), 60% (3/5 partial response [PR]), 84.6% (1/13 complete response [CR] and 10/13 PR), and 25% (1/4 PR), respectively. In the cFAS, median CNS PFS was not reached (95% confidence interval [CI], 8.3 months to not reached), while median CNS PFS in 40-, 80-, 160-, and 240-mg groups were 2.8, 9.7, 19.3 months, and not reached, respectively. Median CNS DoR (19% maturity) in cFAS was not reached (range, 2.8 months to not reached). At 12 months, 50%, 81.8%, and 100% of patients were estimated to remain in response in 80-, 160-, and 240-mg groups, respectively.

      allist table - revised 24-08-2020.jpg

      Conclusion

      AST2818 demonstrated clinically meaningful efficacy against CNS metastases. 160 mg provided relevant benefit with a high CNS ORR and PFS. Further studies are required to confirm these findings.

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