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Yu-Feng Wei



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    MA 16 - Mediastinal, Tracheal and Esophageal Tumor: Multimodality Approaches (ID 675)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
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      MA 16.02 - Different Pattern and Prognostic Role of PD-L1, IDO, and Foxp3 Treg Expression in Thymoma and Thymic Carcinoma (ID 8796)

      15:45 - 17:30  |  Author(s): Yu-Feng Wei

      • Abstract
      • Presentation
      • Slides

      Background:
      The immune checkpoint ligand programmed cell death 1 ligand (PD-L1) is expressed in various tumors, and the expression of indoleamine 2,3-dioxygenase (IDO) and Foxp3 Tregs are associated with tumor-induced tolerance and reported to be responsible for worse survival. Their prognostic role in thymoma and thymic carcinoma, however, has not been investigated.

      Method:
      A tissue microarray comprised of 100 surgically treated thymomas and 69 surgically treated thymic carcinomas was evaluated. PD-L1, IDO, and Foxp3 Treg staining was scored based on intensity as follows: 0 = none, 1 = equivocal/uninterpretable, 2 = weak, and 3 = intermediate-strong. The PD-L1, IDO, and Foxp3 Treg expression score was calculated using a semiquantitive method by multiplying the intensity [0-3] by the staining area [0-100%]. Those cases with all cores scoring three and 2 in more than 50% in the staining area were categorized as PD-L1, IDO, and Foxp3 Treg high expression and the remaining as low expression. Clinical information was also collected on age, sex, Masaoka staging, tumor histology, surgical radicality, and locoregional invasion. Statistical associations were evaluated using χ[2] test and Fisher’s exact test. Progression-free survival and overall survival curves were established by the Kaplan-Meier method and compared using a log-rank test.

      Result:
      Figure 1Figure 2Thirty-six (36%) thymoma and 25 (36%) thymic carcinoma cases revealed high expression of PD-L1. PD-L1 expression in thymoma is significantly associated with Masaoka staging (p<0.001), tumor histology (p<0.001). Although there was a trend toward worse progression-free and overall survival in thymoma and thymic carcinoma with high-expression of PD-L1, only the progression-free survival in thymoma was significantly worse (p=0.024). High expression of IDO was detected in 13 (13%) thymoma and 10 (14%) thymic carcinoma cases, whereas Foxp3 Treg was detected in 16 thymoma (16%) and 20 (29%) thymic carcinoma cases. The expressions of IDO and Foxp3 Treg were significantly associated with tumor histology in thymoma (p=0.002 and 0.016, respectively), but not in thymic carcinoma. Thymic carcinoma with high expression of IDO had a trend toward worse progression-free and overall survival trend (p=0.109 and 0.053, respectively). High expression of Foxp3 Treg, however, was significantly associated with better progression-free survival (p=0.006) and overall survival (p=0.007) in thymic carcinoma.





      Conclusion:
      This is the largest-scale study to evaluate PD-L1 expression in thymic epithelial tumors. Although high expression of PD-L1 might be associated with worse prognosis in thymoma and thymic carcinoma, further investigation into PD-L1, IDO, and Foxp3 Treg should be conducted to benefit anti-PD-L1 immunotherapy for thymic epithelial tumor.

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    P2.07 - Immunology and Immunotherapy (ID 708)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      P2.07-027 - Efficacy and Safety of Nivolumab Therapy for Advanced NSCLC in the Expanded Access Named Patient Program in Taiwan (ID 8711)

      09:30 - 16:00  |  Author(s): Yu-Feng Wei

      • Abstract
      • Slides

      Background:
      Nivolumab is current standard of care for patients with pretreated advanced non-small cell lung cancer (NSCLC). The patients’ and physicians’ experience of using nivolumab in real-world clinical practice in Taiwan is unknown. We aimed to evaluate the efficacy and safety of nivolumab therapy in Taiwan.

      Method:
      We retrospectively reviewed the medical records of the patients with age > 20 years who were diagnosed to have advanced NSCLC and received nivolumab therapy through the Expanded Access Named Patient Program in 2016. Nivolumab 3 mg/kg was administered intravenously every 2 weeks.

      Result:
      A total of 94 patients were included in this analysis. The median age was 60 years (range, 31-76), and 63.8% of these patients were non-smoker. Most of the patients (75.5%) had adenocarcinoma histology, and 34.0% of the patients harbored an EGFR mutation. The median cycle number of nivolumab therapy was 9 (range, 1-28). The median treatment duration was 4.6 months (95% CI, 3.0-6.6). Nivolumab monotherapy is still ongoing in 16 patients (17.0%) on the date of data cutoff. The objective response rate was 13.8%. The median overall survival was 12.0 months (95% CI, 9.2 to not reached). In univariate analysis, sex, age, smoking history, EGFR mutation, squamous histology, and previous extracranial irradiation therapy were not predictors of prolonged survival. Only ECOG performance status (PS) < 2 before starting nivolumab therapy was a predictor of prolonged survival (HR: 0.32; 95% CI, 0.17-0.59). The most common treatment related adverse events (AEs) included fatigue (34.0%), nausea (17.0%), rash (12.8%), asthenia (8.5%), and pyrexia (5.3%). Grade ≧ 3 AEs developed in 7.4% of the patients. All grades interstitial lung disease developed in 4.3% of the patients. One patient died of grade 5 diarrhea after one dose of nivolumab therapy.

      Conclusion:
      The efficacy and safety data in Taiwan were in line with previous clinical trial reports. Patients with PS < 2 may have better survival outcome after receiving nivolumab therapy.

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    P3.01 - Advanced NSCLC (ID 621)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P3.01-016 - Factors Associated with Symptoms Improvement and HRQoL for First-Line EGFR-TKIs in NSCLC: A Multicenter Prospective SMILE Study (ID 8750)

      09:30 - 16:00  |  Presenting Author(s): Yu-Feng Wei

      • Abstract
      • Slides

      Background:
      First-line epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) offer an advantage compared to doublet chemotherapy in progression free survival, tolerability, and quality of life (QOL) in EGFR-mutated advanced non-small cell lung cancer (NSCLC) patients. In Taiwan, gefitinib, erlotinib and afatinib are all reimbursed as first-line therapy. It provides a rare opportunity to investigate factors associated with the extent of symptoms and QOL improvement in real-world patient population.

      Method:
      We conducted a multicenter, prospective, observational study to evaluate the QOL and disease-related symptoms at baseline, 2, 4, and 12 weeks in EGFR-mutated advanced NSCLC patients with first-line EGFR TKI treatment. QOL was assessed by the instrument of Functional Assessment of Cancer Therapy-Lung questionnaire (FACT-L) and Treatment Outcome Index (TOI) derived from FACT-L. Symptoms assessment was evaluated by the Lung Cancer Subscale (LCS). The mean change from baseline of QoL and LCS score was analyzed by paired t-test.

      Result:
      The average age was 65.1± 12.5 (range 31.4–92.9) years old, with a larger proportion of females (62.6%) than males, and more never-smokers (74.0%) than ever-smokers. Patients were treated with gefitinib 250 mg (72.4%), erlotinib 150 mg (18.9%) or afatinib 40 mg (8.7%). For FACT-L, the total score was increased by 4.0 ± 15.49 at week 2, 4.9 ± 18.31 at week 4, and 4.1 ± 20.44 at week 12 (all p<0.001). Similarly, increased TOI of 2.4 ± 11.61 (p<0.001), 3.1 ± 13.48 (p<0.001), and 2.4 ± 14.35 (p=0.009) were observed at week 2, 4, and 12, respectively. For LCS, it was slightly increased by 1.7 ± 4.59 at week 2, 2.0 ± 5.48 at week 4, and 1.9 ± 5.35 at week 12 (all p<0.001). In general, subgroup analyses indicate that patients with more than 2 metastatic sites and ex-smokers were associated with clinically meaningful improvement in terms of LCS (change in LCS ≥ 2 points). Other subgroup analyses show that patients with characteristics such as at least 3 metastatic sites, ex-smoker, PS of 1, and treatment with gefitinib group, were associated with improved QOL in terms of TOI and FACT-L.

      Conclusion:
      In EGFR mutated NSCLC patients, first-line EGFR-TKI treatment was associated with improvement in disease-associated symptoms and QOL. Patients with 2 or more metastatic sites and ex-smokers were associated with symptoms and QOL improvement. In addition, PS of 1 and treatment with gefitinib were associated with clinical meaningful improvement in global QOL.

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