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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林家齊(Chia-Chi Lin) | |
| dc.contributor.author | Pei-Jung Huang | en |
| dc.contributor.author | 黃珮榕 | zh_TW |
| dc.date.accessioned | 2023-03-19T22:25:11Z | - |
| dc.date.copyright | 2022-10-05 | |
| dc.date.issued | 2022 | |
| dc.date.submitted | 2022-08-31 | |
| dc.identifier.citation | Castellanos, E., Feld, E., & Horn, L. (2017). Driven by Mutations: The Predictive Value of Mutation Subtype in EGFR-Mutated Non-Small Cell Lung Cancer. Journal of Thoracic Oncology, 12(4), 612-623. https://doi.org/10.1016/j.jtho.2016.12.014 Gelatti, A., Drilon, A., & Santini, F. C. (2019). Optimizing the sequencing of tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). Lung cancer (Amsterdam, Netherlands), 137, 113-122. https://doi.org/10.1016/j.lungcan.2019.09.017 Hata, A., Katakami, N., Kaji, R., Yokoyama, T., Kaneda, T., Tamiya, M., Inoue, T., Kimura, H., Yano, Y., Tamura, D., Morita, S., Negoro, S., & The Hanshin Oncology Group. (2018). Afatinib plus bevacizumab combination after acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer: multicenter, single-arm, phase 2 trial (ABC study). 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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/84778 | - |
| dc.description.abstract | 目的-本研究針對隨機分派臨床試驗執行系統性文獻回顧和統合分析，探討尚未接受治療帶有表皮生長因子受體突變的晚期非小細胞肺癌以表皮生長因子受體酪胺酸酶抑制劑併用血管內皮生長因子抑制劑與表皮生長因子受體酪胺酸酶抑制劑單獨使用的治療效果以及安全性。 方法-從電子資料庫及相關會議資料搜尋並進行系統性文獻回顧和統合分析。評估指標包含無疾病惡化存活期(PFS)、整體存活期(OS)、客觀反應率(ORR)、疾病控制率(DCR)及不良事件發生率。使用隨機效應模式合併分析結果。 結果-納入八篇臨床試驗結果進行統合分析。以表皮生長因子受體酪胺酸酶抑制劑併用血管內皮生長因子抑制劑與表皮生長因子受體酪胺酸酶抑制劑單獨使用，無疾病惡化存活期在合併治療組較佳，其危險比(Hazard ratio)為0.61; 95% CI, 0.54-0.69; P < 0.0001；整體存活期、客觀反應率和疾病控制率的危險比在統計上沒有顯著的差異；大於或等於等級3之不良事件發生率的風險比(Risk ratio) 為4.23; 95% CI, 2.64-6.78; P<0.00001。 結論-針對尚未接受治療、表皮生長因子受體突變的晚期非小細胞肺癌，以表皮生長因子受體酪胺酸酶抑制劑併用血管內皮生長因子抑制劑與表皮生長因子受體酪胺酸酶抑制劑單獨使用比較，顯著增加無疾病惡化存活期，大於或等於等級3之不良事件發生率也顯著較高。 | zh_TW |
| dc.description.abstract | Purpose-A meta-analysis of randomized controlled trials (RCTs) was conducted to compare the efficacy and safety of EGFR tyrosine kinase inhibitor (EGFR-TKI) plus anti-VEGF/VEGFR antibody with EGFR-TKI monotherapy for the untreated, EGFR-mutated, advanced NSCLC. Methods-PubMed, Embase, Web of Science, and conference proceedings were searched for relevant RCTs. The endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), grade 3-5 adverse events, and serious adverse event (SAE). A random-effects model was used. Results-Data were extracted from eight eligible RCTs. PFS significantly improved in combination therapy compared to monotherapy (HR = 0.61, P < 0.0001) regardless of sex, ECOG PS status, EGFR mutation type (exon 19 deletion or L858R), and brain metastasis status (brain metastasis or no metastasis). There were no statistically significant differences for OS (HR = 0.90, P = 0.19), ORR (RR = 1.27, P = 0.05), and DCR (RR = 1.27, P = 0.45). Conclusion-For patients with untreated, EGFR-mutated, advanced NSCLC, the combination of EGFR-TKI plus anti-VEGF/VEGFR antibody, compared to EGFR-TKI alone, prolonged PFS, but did not improve OS, ORR, and DCR. | en |
| dc.description.provenance | Made available in DSpace on 2023-03-19T22:25:11Z (GMT). No. of bitstreams: 1 U0001-3008202221283700.pdf: 1425548 bytes, checksum: 3307c2825a95e0431ea1b440d5553fbc (MD5) Previous issue date: 2022 | en |
| dc.description.tableofcontents | 口試委員會審定書………………………………………………………………i 致謝………………………………………………………………ii Chinese Abstract………………………………………………………………iii Abstract………………………………………………………………iv Introduction………………………………………………………………1 Methods………………………………………………………………3 Literature Search Strategy………………………………………………………………3 Data Extraction………………………………………………………………4 Quality Assessment and Publication Bias………………………………………………………………4 Statistical Analysis………………………………………………………………5 Results………………………………………………………………6 Study Characteristics………………………………………………………………6 Outcome Measures………………………………………………………………6 PFS………………………………………………………………6 OS………………………………………………………………7 ORR and DCR………………………………………………………………7 Incidence of Grade ≥ 3 AEs and SAEs………………………………………………………………8 Discussion………………………………………………………………9 Conclusion………………………………………………………………11 Reference………………………………………………………………12 Tables and Figures………………………………………………………………17 Figure 1 PRISMA Flow Diagram………………………………………………………………17 Table 1 Patient Characteristics of Included RCTs………………………………………………………………18 Table 2 Clinical Data of Included RCTs………………………………………………………………19 Table 3 The Risk of Bias Assessment of Included RCTs………………………………………………………………20 Figure 2 Effect of Treatment on Progression-Free Survival (PFS) in All Groups………………………………………………………………21 Figure 3 Effect of Treatment on Progression-Free Survival (PFS) in Subgroups………………………………………………………………22 Figure 4 Effect of Treatment on Progression-Free Survival (PFS) in Subgroups………………………………………………………………23 Figure 5 Effect of Treatment on Median Overall Survival (OS) in All Groups and Subgroups………………………………………………………………24 Figure 6 Effect of Treatment on ORR in All Groups and Subgroups………………………………………………………………25 Figure 7 Effect of Treatment on DCR in All Groups and Subgroups………………………………………………………………26 Figure 8 Grade ≥ 3 Adverse Events in All Groups and Subgroups………………………………………………………………27 Table 4 The Pooled Incidence of Grade ≥ 3 Adverse Events………………………………………………………………28 Figure 9 Serious Adverse Event in All Groups and Subgroups………………………………………………………………29 Figure 10 Funnel Plot of Progression-Free Survival (PFS)………………………………………………………………30 Figure 11 Effect of Treatment on Progression-Free Survival (PFS) in All Groups (combine AfaBev-CS study)………………………………………………………………30 Protocol………………………………………………………………31 1. Synopsis………………………………………………………………32 2. Table of Contents………………………………………………………………36 3. Abbreviations and Definitions………………………………………………………………43 4. Introduction………………………………………………………………45 4.1. Use of EGFR-TKI in Advanced NSCLC………………………………………………………………45 4.2. EGFR-TKI in Combination with Anti-VEGF/VEGFR Antibody………………………………………………………………45 4.3. Study Rationale and Benefit-Risk Assessment………………………………………………………………46 5. Objectives………………………………………………………………48 5.1. Primary Objective………………………………………………………………48 5.2. Secondary Objectives………………………………………………………………48 6. Study Population………………………………………………………………49 6.1. Inclusion Criteria………………………………………………………………49 6.2. Exclusion Criteria………………………………………………………………51 6.3. Study Enrollment and Treatment Assignment………………………………………………………………53 6.4. Withdrawal of Consent………………………………………………………………54 6.5. Discontinuation of Study Treatment………………………………………………………………54 6.6. Discontinuation from the Study Participation………………………………………………………………55 6.7. Patients Who Are Lost to Follow-up………………………………………………………………55 7. Investigational Plan………………………………………………………………56 7.1. Summary of Study Design………………………………………………………………56 7.2. Baseline and Study Treatment Period………………………………………………………………56 7.2.1. Medical History and Medications………………………………………………………………57 7.2.2. Demography………………………………………………………………57 7.2.3. Vital Signs………………………………………………………………57 7.2.4. Physical Examinations………………………………………………………………57 7.2.5. ECOG Performance Status………………………………………………………………57 7.2.6. Toxicity/AE………………………………………………………………57 7.2.7. Clinical Tests………………………………………………………………58 7.2.8. Electrocardiograms………………………………………………………………58 7.2.9. Efficacy Assessments………………………………………………………………58 7.3. End of Treatment………………………………………………………………58 7.4. Post-Discontinuation Follow-Up Period………………………………………………………………59 7.5. Study Completion and End of Trial………………………………………………………………59 7.6. Study Duration………………………………………………………………59 8. Treatment………………………………………………………………60 8.1. Treatments Administered………………………………………………………………60 8.1.1. Premedication………………………………………………………………61 8.2. Study Drugs………………………………………………………………61 8.2.1. Erlotinib………………………………………………………………61 8.2.2. Bevacizumab………………………………………………………………61 8.2.3. Ramucirumab………………………………………………………………61 8.3. Storage and Preparation………………………………………………………………61 8.3.1. Erlotinib Storage and Preparation………………………………………………………………61 8.3.2. Bevacizumab Storage and Preparation………………………………………………………………61 8.3.3. Ramucirumab Storage and Preparation………………………………………………………………62 8.4. Dose Delays or Dose Modifications………………………………………………………………62 8.4.1. Dose Delays and Dose Modifications for Erlotinib………………………………………………………………62 8.4.2. Dose Delays and Dose Modifications for Bevacizumab………………………………………………………………63 8.4.3. Dose Delays and Dose Modifications for Ramucirumab………………………………………………………………64 8.5. Concomitant Therapy………………………………………………………………65 8.6. Prohibited and Restricted Concomitant Therapy………………………………………………………………65 8.6.1. CYP3A4 Inducers or Strong Inhibitors………………………………………………………………65 8.6.2. Anticoagulants………………………………………………………………66 8.6.3. H2-Receptor Antagonists and Antacids………………………………………………………………66 8.6.4. Proton Pump Inhibitors………………………………………………………………66 8.7. Other Study Conditions: Surgery and Palliative Radiotherapy (or Equally Considered Procedure) During Study Treatment Period………………………………………………………………66 8.7.1. Surgery………………………………………………………………66 8.7.2. Radiotherapy………………………………………………………………66 8.8. Treatment Compliance………………………………………………………………66 9. Efficacy Measures, Safety Assessments, Patient-Reported Outcomes, Sample Collection and Testing, Appropriateness of Measurements………………………………………………………………68 9.1. Efficacy Measures………………………………………………………………68 9.1.1. Primary Efficacy Measure………………………………………………………………68 9.1.2. Secondary Efficacy Measures………………………………………………………………69 9.2. Safety Assessments………………………………………………………………69 9.2.1. Adverse Events………………………………………………………………69 9.2.2. Serious Adverse Events………………………………………………………………70 9.2.3. Suspected Unexpected Serious Adverse Reactions………………………………………………………………71 9.3. Patient-Reported Outcomes………………………………………………………………71 9.4. Sample Collection and Testing………………………………………………………………72 9.5. Appropriateness of Measurements………………………………………………………………72 10. Data Quality Assurance………………………………………………………………73 10.1. Data Capture System………………………………………………………………73 11. Sample Size and Statistical Methods………………………………………………………………74 11.1. Determination of Sample Size………………………………………………………………74 11.2. Statistical and Analytical Plans………………………………………………………………74 11.2.1. General Considerations………………………………………………………………74 11.2.2. Analysis Populations………………………………………………………………74 11.2.3. Patient Disposition………………………………………………………………74 11.2.4. Patient Characteristics………………………………………………………………75 11.2.5. Treatment Compliance………………………………………………………………75 11.2.6. Primary Outcome and Methodology………………………………………………………………75 11.2.7. Secondary Outcome and Methodology………………………………………………………………76 11.2.7.1. Overall Survival………………………………………………………………76 11.2.7.2. Objective Response Rate and Disease Control Rate………………………………………………………………77 11.2.7.3. Safety Analyses………………………………………………………………77 11.2.7.4. Patient-Reported Outcomes Analyses………………………………………………………………77 11.2.8. Sensitivity Analyses………………………………………………………………77 11.2.9. Subgroup Analyses………………………………………………………………78 11.2.10. Primary Analysis………………………………………………………………78 12. Informed Consent, Ethical Review, and Regulatory Considerations………………………………………………………………79 12.1. Inform Consent………………………………………………………………79 12.2. Ethical Review………………………………………………………………79 12.3. Regulatory Considerations………………………………………………………………79 13. References………………………………………………………………81 Table 1 ECOG Performance Status Scale………………………………………………………………56 Table 2 Treatment Regimens and Dosing Schedule………………………………………………………………59 Table 3 Erlotinib Dose Reduction Schedule………………………………………………………………62 Table 4 Secondary Efficacy Endpoints………………………………………………………………68 Figure 1 Illustration of Study Design………………………………………………………………56 Attachment 1 Arm A (erlotinib plus bevacizumab) Study Schedule………………………………………………………………86 Attachment 2 Arm B (erlotinib plus ramucirumab) Study Schedule………………………………………………………………89 Attachment 3 CYP3A4 Modulators………………………………………………………………92 Attachment 4 Laboratory Assessments………………………………………………………………92 | |
| dc.language.iso | en | |
| dc.title | 表皮生長因子受體酪胺酸酶抑制劑併用血管內皮生長因子抑制劑在未接受治療、EGFR突變、晚期非小細胞肺癌:系統性回顧和統合分析、第三期臨床試驗計畫書 | zh_TW |
| dc.title | EGFR Tyrosine Kinase Inhibitor Plus Anti-VEGF/VEGFR Antibody in Patients with untreated, EGFR-Mutated, Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis, A Phase III Clinical Trial Protocol | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 110-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 何肇基(Chao-Chi Ho),施金元(Jin-Yuan Shih) | |
| dc.subject.keyword | 表皮生長因子受體酪胺酸酶抑制劑,血管內皮生長因子抑制劑,統合分析,晚期非小細胞肺癌, | zh_TW |
| dc.subject.keyword | EGFR tyrosine kinase inhibitor,anti-VEGF/VEGFR antibody,meta-analysis,advanced non-small cell lung cancer, | en |
| dc.relation.page | 92 | |
| dc.identifier.doi | 10.6342/NTU202202991 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2022-09-01 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 臨床醫學研究所 | zh_TW |
| dc.date.embargo-lift | 2022-10-05 | - |
| 顯示於系所單位： | 臨床醫學研究所 | |
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