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Jianjiao Ni



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

    • Event: WCLC 2020
    • Type: Posters
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 2
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P76.13 - Osimertinib Delays but Not Prevents Central Nervous System Metastasis in EGFR-Mutant Advanced Non-Small Cell Lung Cancer (ID 1135)

      00:00 - 00:00  |  Presenting Author(s): Jianjiao Ni

      • Abstract
      • Slides

      Introduction

      Central nervous system (CNS) is a common site of EGFR Tyrosine kinase inhibitor (TKI) treatment failure in advanced non-small cell lung cancer (NSCLC). Various EGFR TKIs with distinct potencies against CNS metastasis are approved. This study aims to compare the incidence of symptomatic CNS metastasis in advanced EGFR-mutant NSCLC without baseline CNS lesions and receiving first- or third-generation EGFR TKIs.

      Methods

      Patients with EGFR-mutant advanced NSCLC without baseline CNS metastasis and receiving standard of care EGFR-TKIs were included. Cumulative incidences of symptomatic CNS metastasis upon EGFR-TKI treatment failure were calculated using the Kaplan-Meier method and significant risk factors of CNS metastasis were identified using the Cox proportional hazards models. Furthermore, radiographic features and clinical outcomes of patients who developed CNS metastasis were analyzed.

      Results

      Among 935 patients enrolled, 633, 143 and 35 received first-line gefitinib, erlotinib and osimertinib, respectively, and the remaining 124 received second-line Osimertinib. At a median follow-up of 10 months (range, 1-93 months), 517 patients developed EGFR-TKI treatment failure, of whom 45 had symptomatic CNS metastasis. The 1-, 2- and 3-year cumulative incidences of symptomatic CNS metastasis were 4.2%, 7.9% and 14.4%, respectively. There was no difference of developing symptomatic CNS metastasis among patients receiving gefitinib or erlotinib (p=0.857), while patients receiving osimertinib (Group B) had a significant lower risk than those receiving first-generation EGFR-TKIs (Group A) (HR 0.45; 95%CI 0.20-0.99, p=0.049). Of note, the survival curves tended to reach a plateau after three years, and the cumulative incidence of symptomatic CNS metastasis beyond that time, as well as the percentage of patients who developed symptomatic CNS metastasis among those who had EGFR-TKI treatment failure, was similar in Group A and Group B. Patients harboring L858R mutation had a higher risk developing symptomatic CNS metastasis than patients harboring other types of sensitizing EGFR mutations (p=0.003). Among 45 patients who developed symptomatic CNS metastasis, 20 had single cranial lesion, 39 had a largest tumor lesion smaller than 3cm and 39 had metastatic lesion outside the hippocampus region. Moreover, among the 45 patients, median overall survival (OS) calculated from the diagnosis of advanced disease was 33.3 (95%CI 24.8-41.8) months, and patients with single cranial lesion had a significantly longer OS (p=0.011).figure.jpg

      Conclusion

      Compared with first-generation EGFR-TKIs, osimertinib significantly delays the development of symptomatic CNS metastasis in EGFR-mutant advanced NSCLC and L858R mutation is an independent risk factor of CNS metastasis.

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      P76.82 - Osimertinib versus First-Generation EGFR-TKIs in Untreated EGFR-Mutant NSCLC with Brain Metastasis: 362 Real-World Cases (ID 3515)

      00:00 - 00:00  |  Presenting Author(s): Jianjiao Ni

      • Abstract
      • Slides

      Introduction

      Osimertinib showed superior efficacy to first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) among untreated advanced EGFR-mutant non-small cell lung cancer (NSCLC) in the phase III FLAURA study. However, relevant real-world data in patients with baseline brain metastasis (BM) as well as the clinical value of upfront cranial local therapy (CLT) remain scarce.

      Methods

      Untreated EGFR-mutant NSCLC patients with BMs receiving first-line Osimertinib or first-generation EGFR-TKIs at our cancer center were retrospectively enrolled. Progression-free survival (PFS), intracranial PFS (iPFS) and overall survival (OS) were calculated in the entire cohort and patient groups created by propensity score matching (PSM). Survival outcomes and pattern of treatment failure were also investigated in patient subgroups stratified by the status of BMs, which was classified as oligo-BM (number≤3 and size≤3cm) and multiple-BM (number≥4 or size>3cm).

      Results

      Among the 362 patients enrolled, 265 received first-generation EGFR-TKIs (Gefitinib=196, Erlotinib=69) and the rest 97 received Osimertinib. Patients receiving first-line Osimertinib had more (p<0.001) and larger BMs (p=0.011) than those receiving first-generation EGFR-TKIs. With a median follow-up of 17.1 months (range, 2.6-73 months), median PFS and OS was 14.6 months and 31 months, respectively. Patient groups (Osimertinib=97, first-generation group=97) were created by PSM with balanced clinic-pathological parameters, and iPFS (32.5 vs 8.4 months, p<0.001) , PFS (34.7 vs 11.5months,p<0.001) and OS (40.6 vs 23.8 months, p=0.041) were significantly longer in the Osimertinib group (Figure a-c). Upfront CLT, including surgery, whole brain radiotherapy and stereotactic radiotherapy (SRS), was performed in 129 patients before disease progression and it prolonged iPFS and PFS, but not OS, in the entire cohort. Among patients with baseline oligo-BMs (n=195), upfront CLT (dominated by SRS) improved iPFS (HR=0.443, p=0.001), PFS (HR=0.373, p<0.001) and OS (HR=0.795, p=0.035) (Figure d-f), which was not the case among patients with baseline multiple-BMs. Pattern of failure analyses indicated that more patients with baseline multiple-BMs turned into the status of oligo-BMs at the maximal response to EGFR-TKIs (p=0.023) and less patients developed progressive disease in the central nervous system (p=0.019) among patients receiving upfront CTL than those didn't. Of note, 8 patients with oligo-BMs but didn't receive upfront CLT developed multiple progressive disease in the brain.

      figure.jpg

      Conclusion

      To the best of our knowledge, this is the first real-world study with considerable sample size verifying the superior efficacy of first-line Osimertinib treatment in EGFR-mutant NSCLC with BMs. Additionally, upfront brain SRS was recommended for those with oligo-BMs.

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