Comparative Efficacy of Systemic Agents for Brain Metastases From Non-Small-Cell Lung Cancer With an EGFR Mutation/ALK Rearrangement: A Systematic Review and Network Meta-Analysis
BackgroundBrain metastases (BM) from non-small-cell lung cancer (NSCLC) are frequent and carry significant morbidity, and current management options include varying local and systemic therapies. Here, we performed a systematic review and network meta-analysis to determine the ideal treatment regimen...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.739765/full |
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| author | Shervin Taslimi Karanbir Brar Yosef Ellenbogen Jiawen Deng Winston Hou Fabio Y. Moraes Michael Glantz Michael Glantz Brad E. Zacharia Brad E. Zacharia Aaron Tan Manmeet S. Ahluwalia Manmeet S. Ahluwalia Mustafa Khasraw Gelareh Zadeh Alireza Mansouri Alireza Mansouri |
| author_facet | Shervin Taslimi Karanbir Brar Yosef Ellenbogen Jiawen Deng Winston Hou Fabio Y. Moraes Michael Glantz Michael Glantz Brad E. Zacharia Brad E. Zacharia Aaron Tan Manmeet S. Ahluwalia Manmeet S. Ahluwalia Mustafa Khasraw Gelareh Zadeh Alireza Mansouri Alireza Mansouri |
| author_sort | Shervin Taslimi |
| collection | DOAJ |
| description | BackgroundBrain metastases (BM) from non-small-cell lung cancer (NSCLC) are frequent and carry significant morbidity, and current management options include varying local and systemic therapies. Here, we performed a systematic review and network meta-analysis to determine the ideal treatment regimen for NSCLC BMs with targetable EGFR-mutations/ALK-rearrangements.MethodsWe searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CENTRAL and references of key studies for randomized controlled trials (RCTs) published from inception until June 2020. Comparative RCTs including ≥10 patients were selected. We used a frequentist random-effects model for network meta-analysis (NMA) and assessed the certainty of evidence using the GRADE approach. Our primary outcome of interest was intracranial progression-free survival (iPFS).ResultsWe included 24 studies representing 19 trials with 1623 total patients. Targeted tyrosine kinase inhibitors (TKIs) significantly improved iPFS, with second-and third- generation TKIs showing the greatest benefit (HR=0.25, 95%CI 0.15-0.40). Overall PFS was also improved compared to conventional chemotherapy (HR=0.47, 95%CI 0.36-0.61). In EGFR-mutant patients, osimertinib showed the greatest benefit in iPFS (HR=0.32, 95%CI 0.15-0.69) compared to conventional chemotherapy, while gefitinib + chemotherapy showed the greatest overall PFS benefit (HR=0.26, 95%CI 0.10-0.70). All ALKi improved overall PFS compared to conventional chemotherapy, with alectinib having the greatest benefit (HR=0.13, 95%CI 0.07-0.24).ConclusionsIn patients with NSCLC BMs and EGFR/ALK mutations, targeted TKIs improve intracranial and overall PFS compared to conventional modalities such as chemotherapy, with greater efficacy seen using newer generations of TKIs. This data is important for treatment selection and patient counseling, and highlights areas for future RCT research.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=179060. |
| first_indexed | 2024-12-14T13:32:30Z |
| format | Article |
| id | doaj.art-800fef5f8cd54d518b149439d031f6cb |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-14T13:32:30Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-800fef5f8cd54d518b149439d031f6cb2022-12-21T22:59:40ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-12-011110.3389/fonc.2021.739765739765Comparative Efficacy of Systemic Agents for Brain Metastases From Non-Small-Cell Lung Cancer With an EGFR Mutation/ALK Rearrangement: A Systematic Review and Network Meta-AnalysisShervin Taslimi0Karanbir Brar1Yosef Ellenbogen2Jiawen Deng3Winston Hou4Fabio Y. Moraes5Michael Glantz6Michael Glantz7Brad E. Zacharia8Brad E. Zacharia9Aaron Tan10Manmeet S. Ahluwalia11Manmeet S. Ahluwalia12Mustafa Khasraw13Gelareh Zadeh14Alireza Mansouri15Alireza Mansouri16Division of Neurosurgery, Department of Surgery, Queen’s University, Kingston, ON, CanadaFaculty of Medicine, University of Toronto, Toronto, ON, CanadaDivision of Neurosurgery, Department of Surgery, Queen’s University, Kingston, ON, CanadaFaculty of Health Sciences, McMaster University, Hamilton, ON, CanadaFaculty of Health Sciences, McMaster University, Hamilton, ON, CanadaDepartment of Oncology, Queen’s University, Kingston, ON, CanadaDepartment of Neurosurgery, Penn State Health, Hershey, PA, United States Penn State Cancer Institute, Hershey, PA, United StatesDepartment of Neurosurgery, Penn State Health, Hershey, PA, United States Penn State Cancer Institute, Hershey, PA, United StatesDivision of Medical Oncology, National Cancer Center Singapore, Singapore, SingaporeRose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, United StatesDepartment of Hematology/Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, United States0The Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, United StatesDivision of Neurosurgery, Department of Surgery, Queen’s University, Kingston, ON, CanadaDepartment of Neurosurgery, Penn State Health, Hershey, PA, United States Penn State Cancer Institute, Hershey, PA, United StatesBackgroundBrain metastases (BM) from non-small-cell lung cancer (NSCLC) are frequent and carry significant morbidity, and current management options include varying local and systemic therapies. Here, we performed a systematic review and network meta-analysis to determine the ideal treatment regimen for NSCLC BMs with targetable EGFR-mutations/ALK-rearrangements.MethodsWe searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CENTRAL and references of key studies for randomized controlled trials (RCTs) published from inception until June 2020. Comparative RCTs including ≥10 patients were selected. We used a frequentist random-effects model for network meta-analysis (NMA) and assessed the certainty of evidence using the GRADE approach. Our primary outcome of interest was intracranial progression-free survival (iPFS).ResultsWe included 24 studies representing 19 trials with 1623 total patients. Targeted tyrosine kinase inhibitors (TKIs) significantly improved iPFS, with second-and third- generation TKIs showing the greatest benefit (HR=0.25, 95%CI 0.15-0.40). Overall PFS was also improved compared to conventional chemotherapy (HR=0.47, 95%CI 0.36-0.61). In EGFR-mutant patients, osimertinib showed the greatest benefit in iPFS (HR=0.32, 95%CI 0.15-0.69) compared to conventional chemotherapy, while gefitinib + chemotherapy showed the greatest overall PFS benefit (HR=0.26, 95%CI 0.10-0.70). All ALKi improved overall PFS compared to conventional chemotherapy, with alectinib having the greatest benefit (HR=0.13, 95%CI 0.07-0.24).ConclusionsIn patients with NSCLC BMs and EGFR/ALK mutations, targeted TKIs improve intracranial and overall PFS compared to conventional modalities such as chemotherapy, with greater efficacy seen using newer generations of TKIs. This data is important for treatment selection and patient counseling, and highlights areas for future RCT research.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=179060.https://www.frontiersin.org/articles/10.3389/fonc.2021.739765/fulltargeted therapybrain metastasesnon-small cell lung cancerneuro-oncologyEGFR inhibitorsALK inhibitors |
| spellingShingle | Shervin Taslimi Karanbir Brar Yosef Ellenbogen Jiawen Deng Winston Hou Fabio Y. Moraes Michael Glantz Michael Glantz Brad E. Zacharia Brad E. Zacharia Aaron Tan Manmeet S. Ahluwalia Manmeet S. Ahluwalia Mustafa Khasraw Gelareh Zadeh Alireza Mansouri Alireza Mansouri Comparative Efficacy of Systemic Agents for Brain Metastases From Non-Small-Cell Lung Cancer With an EGFR Mutation/ALK Rearrangement: A Systematic Review and Network Meta-Analysis Frontiers in Oncology targeted therapy brain metastases non-small cell lung cancer neuro-oncology EGFR inhibitors ALK inhibitors |
| title | Comparative Efficacy of Systemic Agents for Brain Metastases From Non-Small-Cell Lung Cancer With an EGFR Mutation/ALK Rearrangement: A Systematic Review and Network Meta-Analysis |
| title_full | Comparative Efficacy of Systemic Agents for Brain Metastases From Non-Small-Cell Lung Cancer With an EGFR Mutation/ALK Rearrangement: A Systematic Review and Network Meta-Analysis |
| title_fullStr | Comparative Efficacy of Systemic Agents for Brain Metastases From Non-Small-Cell Lung Cancer With an EGFR Mutation/ALK Rearrangement: A Systematic Review and Network Meta-Analysis |
| title_full_unstemmed | Comparative Efficacy of Systemic Agents for Brain Metastases From Non-Small-Cell Lung Cancer With an EGFR Mutation/ALK Rearrangement: A Systematic Review and Network Meta-Analysis |
| title_short | Comparative Efficacy of Systemic Agents for Brain Metastases From Non-Small-Cell Lung Cancer With an EGFR Mutation/ALK Rearrangement: A Systematic Review and Network Meta-Analysis |
| title_sort | comparative efficacy of systemic agents for brain metastases from non small cell lung cancer with an egfr mutation alk rearrangement a systematic review and network meta analysis |
| topic | targeted therapy brain metastases non-small cell lung cancer neuro-oncology EGFR inhibitors ALK inhibitors |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.739765/full |
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