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Li Mao



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    FP14 - Targeted Therapy - Clinically Focused (ID 252)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 2
    • 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): Li Mao

      • 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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      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  |  Author(s): Li Mao

      • Abstract

      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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    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): Li Mao

      • 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.