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Xuezhi Hao



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    EP1.12 - Small Cell Lung Cancer/NET (ID 202)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.12-11 - Effect of Treatment Mode on Prognosis of Resectable Limited-Stage Small Cell Lung Cancer (Now Available) (ID 1808)

      08:00 - 18:00  |  Author(s): Xuezhi Hao

      • Abstract
      • Slides

      Background

      The optimal choice of post-operative treatment mode for resectable limited-stage small cell lung cancer (SCLC) is controversial in clinical practice. Different treatment modes may have different effects on prognosis of small cell lung cancer after resection.

      Method

      Data from a total of 122 patients with limited-stage SCLC undergoing operation were collected at our Cancer Hospital from 2012 to 2016. Clinical and pathological features, and treatment modes (including surgical methods, postoperative adjuvant radiotherapy and chemotherapy, prophylactic brain radiotherapy, etc.) were compared in small cell lung cancer after resection .The survival outcomes among different factors were analyzed by Kaplan-Meier method, and the survival differences among different factors were compared by log-rank method. Multivariate cox regression analysis was used to explore independent prognostic factors.

      Result

      The median follow-up time was 54.23 months. Among 122 patients, the 1-, 3- and 5-year overall survival (OS) rates were 95.08%, 75.14% and 63.79%, respectivly. The 1-, 3- and 5-year recurrence-free survival (RFS) rates were 80.99%, 66.62% and 61.86%, respectively. Recurrences were diagnosed in 56 (45%) patients, including 22 (39%) with brain metastasis, 15 (27%) with intrapulmonary recurrence, 7 (13%) with bone metastasis, 6 (11%) with hepatic metastasis, and 6 (11%) with other metastasis. Operation patterns affected OS. 116 patients received lobectomy and 6 patients received pneumonectomy. Median OS of these two groups were 68.37 and 35.37 months, respectively (p = 0.028). The T stage affected the postoperative OS. The median OS of T1、T2、T3 were 65.87, 71.29 and 29.92 months, respectively (p = 0.021). The disease-free survival (PFS) and OS of patients receiving adjuvant chemotherapy or combined with radiotherapy were longer than those receiving surgery only. The median PFS of adjuvant chemotherapy group, chemotherapy and radiotherapy combination group, and simple surgery group were 69.01,53.87 and 19.37 months, respectively (p=0.002). Accordingly, the median OS were 70.6, 65.56 and 30.8 months (p=0.002). Patients with postoperative prophylactic cranial irradiation (PCI) had a longer OS than those without PCI (62.28 vs. 78.84 months, p=0.028).

      Conclusion

      As for patients with resectable limited-stage SCLC,the 5-year survival rate of patients with surgery is higher than those without. Lobectomy is the optimal surgery mode, and adjuvant chemotherapy combined with prophylactic cranial irradiation after operation can significantly prolong the OS.

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    EP1.14 - Targeted Therapy (ID 204)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.14-19 - Efficacy and Safety of Afatinib for Advanced Lung Adenocarcinoma Patients with Sensitive EGFR Mutations in Chinese Population (Now Available) (ID 817)

      08:00 - 18:00  |  Author(s): Xuezhi Hao

      • Abstract
      • Slides

      Background

      Afatinib is an irreversible ErbB family blocker that improves progression-free survival (PFS) of advanced EGFR-mutant lung adenocarcinoma, comparing with chemotherapy. However, afatinib leads to more adverse events than first-generation EGFR inhibitors. Hence, exploration of optimal afatinib initial dose and its efficacy and safety for Asian patients has drawn extensive attention.

      Method

      We retrospectively investigated advanced NSCLC patients treated with afatinib from February 27, 2017 to October 30, 2018. Demographic and clinical information, survival data and adverse events were collected and evaluated.

      Result

      A total of 60 patients were included into this study. Thirty-nine (65%) patients received afatinib as first-line treatment. Median PFS for first-line afatinib treatment was 15.64 months [95% confidence internal (CI), not reached] and median OS has not been reached. When including age, sex, smoking history, baseline brain metastasis status, afatinib starting dose and mutation types into a multivariate COX regression analysis, PFS of patients with common sensitive EGFR mutations only was significantly longer than that of patients with uncommon mutations [hazard ratio (HR), 0.256; 95%CI, 0.080-0.823; p=0.022]. No significant difference was observed in median PFS between patients treated with a starting dose of 40mg and 30mg (11.18 vs. 5.25 months, p=0.060). The incidence of all grades rash/acne (92.5% vs. 61.1%, p=0.011) and paronychia (82.5% vs. 50.0%, p=0.010) of 40mg group was significantly higher than that of 30mg group.figure 1.jpg

      Table 1. Afatinib-Related Adverse Events

      Adverse events

      All Patients

       

      Afatinib 40mg

       

      Afatinib 30mg

       

      N=58

      N=40

      N=18

      N

      %

       

      N

      %

       

      N

      %

      p

      Diarrhea

      50

      86.2

      36

      90.0

      14

      77.8

      0.402

      ≥Grade 3

      6

      10.3

      5

      12.5

      1

      5.6

      0.736

      Rash/acne

      48

      82.8

      37

      92.5

      11

      61.1

      0.011

      ≥Grade 3

      2

      3.4

      2

      5.0

      0

      0.0

      1.000

      Paronychia

      42

      72.4

      33

      82.5

      9

      50.0

      0.010

      ≥Grade 3

      2

      3.4

      2

      5.0

      0

      0.0

      1.000

      Stomatitis/mucositis

      41

      70.7

      29

      72.5

      12

      66.7

      0.652

      ≥Grade 3

      0

      0.0

      0

      0.0

      0

      0.0

      -

      Dry skin

      22

      37.9

      16

      40.0

      6

      33.3

      0.628

      ≥Grade 3

      0

      0.0

      0

      0.0

      0

      0.0

      -

      Pruritus

      9

      15.5

      7

      17.5

      2

      11.1

      0.818

      ≥Grade 3

      0

      0.0

       

      0

      0.0

       

      0

      0.0

      -

      Conclusion

      First-line afatinib treatment is beneficial to advanced lung adenocarcinoma with sensitive EGFR mutations. Initial dose and baseline brain metastasis status do not impact PFS significantly.

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    P1.01 - Advanced NSCLC (ID 158)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.01-91 - Clinical Outcomes of Various Resistance Mechanisms of Osimertinib in Chinese Advanced Non-Small Cell Lung Cancer Patients (Now Available) (ID 1264)

      09:45 - 18:00  |  Author(s): Xuezhi Hao

      • Abstract
      • Slides

      Background

      Increasing efforts have been invested in elucidating the resistance mechanisms to osimertinib. Major resistance mechanisms include but not limited to acquired EGFR mutations, predominantly C797, mutations in bypass pathways and small cell lung cancer (SCLC) transformation. However, no study has comprehensively investigated clinical outcomes of various mechanisms of resistance.

      Method

      103 T790M positive advanced Chinese non-small cell lung cancer (NSCLC) patients who progressed on 1st generation EGFR-TKI were enrolled. Targeted sequencing, using a panel consisting of 168 lung cancer related genes, was performed on paired plasma samples collected prior to osimertinib and after the development of disease progression (PD) to profile mutation spectrum. 7 patients with no mutation detected at PD were excluded from analyses.

      Result

      Major acquired mutations included 25% EGFR mutations, predominantly C797 and L792, 16% MET amplification, 8% TP53 mutations, 4% KRAS mutations, 4% RET fusions, 4% ERBB2 amplification and 6.25% RB1 mutations. Acquired RB1 mutation may indicate the possibility of SCLC transformation. Approximately, 30% of patients with no known resistance mechanisms at PD. In this cohort, we had 61 patients with 19 deletion and 35 patients with EGFR L858R prior to the initiation of osimertinib. We revealed patients with 19del acquired more mutations (p=0.014) and were more likely to acquire mutations in MAP/PI3Kpathway (p=0.04) and TP53 at PD (p=0.021). On the other hand, acquired ERBB2 amplifications were only detected in L858R-mutant patients (p=0.047). Furthermore, 36 patients preserved T790M and 60 patients lost T790M at PD. Our data revealed patients retaining T790M, often associated with activation of bypass signaling pathways or continued EGFR activation through tertiary mutations, had a longer progression-free survival (PFS) (p=0.047) and overall survival (OS) (p=0.04) comparing to patients with T790M loss, often with diverse and EGFR-independent mechanisms. We also show that patients with acquired C797S had significantly longer PFS (p=0.031), while patients with acquired MET amplifications had significantly shorter PFS (p=0.033).

      Conclusion

      Collectively, we revealed differential clinical outcomes associated with various resistance mechanisms, representing an important step in advancing the understanding of resistance mechanisms of osimertinib.

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    P2.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 187)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.16-08 - Clinical Characteristics and Outcomes of Patients with BRAF Mutated Non-Small Cell Lung Cancer (Now Available) (ID 1106)

      10:15 - 18:15  |  Author(s): Xuezhi Hao

      • Abstract
      • Slides

      Background

      BRAF mutation is a driver oncogene identified in 0.5-2% of non-small cell lung cancer (NSCLC) patients in China, and clinical data are relatively inadequate. This study assessed the clinical characteristics, course of disease and treatment outcomes in patients with BRAF mutated NSCLC in a real-world setting.

      Method

      Between Apr 1, 2017 and Feb 1, 2019, medical data of patients with NSCLC harboring BRAF mutation in our cancer center was retrospective collected. Patient characteristics and treatment outcomes were reviewed. Data cutoff was Apr 1, 2019.

      Result

      A total of 36 patients were identified. BRAF V600E was the most common (31/36, 86.1%), other BRAF molecular subsets were observed in 5 (13.9%) cases including K601E, G469V, G596R and D594N. The majority of patients with BRAF mutation were female (20/36, 55.6%) and non-smokers (20/36, 55.6%), all of them were adenocarcinoma, and median age at diagnosis was 56 (range, 33-79). Twenty-seven patients were recurrent or metastatic NSCLC at data cutoff, most of whom received chemotherapy (16/27, 59.3%) as first-line therapy with median progression-free survival (PFS) of 9.8 months (95%CI 0.0, 21.5) and disease control rate (DCR) of 68.8% (11/16). Eight patients received anti-BRAF targeted therapy (including dabrafenib, trametinib and vemurafenib) in the first-line and showed superior efficacy than those received chemotherapy (median PFS, 15.9 months [95%CI, 4.5, 27.3] vs. 9.8 months [95%CI, 0.0, 21.5], P = 0.183; DCR, 100% vs. 68.8%, P = 0.130). As for distinct molecular subsets, most patients with V600E mutation were female (19/31, 61.3%) and non-smokers (19/31, 61.3%), while four of five (80.0%) patients with non-V600E mutation were male and smokers. All of the 3 patients in non-V600E mutations subgroup with recurrent or metastatic disease received chemotherapy in the first-line, and achieved 2 of SD, 1 of PD.

      efficacy.jpg

      Conclusion

      NSCLC with BRAF mutation was associated with specific characteristics, which were variable between molecular subsets. BRAF inhibitors should be considered firstly in treating patients with BRAF-mutated lung cancers. The prognosis value of non-V600E mutations and treatment selection needs more research.

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