Comparative Effectiveness of Second-Line Targeted Therapies for Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-Analysis of Real-World Observational Studies.
<h4>Objective</h4>The optimal sequencing of targeted therapies for metastatic renal cell carcinoma (mRCC) is unknown. Observational studies with a variety of designs have reported differing results. The objective of this study is to systematically summarize and interpret the published re...
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Public Library of Science (PLoS)
2014-01-01
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| Online Access: | https://doi.org/10.1371/journal.pone.0114264 |
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| author | Daniel Y Heng James Signorovitch Elyse Swallow Nanxin Li Yichen Zhong Paige Qin Daisy Y Zhuo Xufang Wang Jinhee Park Sotirios Stergiopoulos Christian Kollmannsberger |
| author_facet | Daniel Y Heng James Signorovitch Elyse Swallow Nanxin Li Yichen Zhong Paige Qin Daisy Y Zhuo Xufang Wang Jinhee Park Sotirios Stergiopoulos Christian Kollmannsberger |
| author_sort | Daniel Y Heng |
| collection | DOAJ |
| description | <h4>Objective</h4>The optimal sequencing of targeted therapies for metastatic renal cell carcinoma (mRCC) is unknown. Observational studies with a variety of designs have reported differing results. The objective of this study is to systematically summarize and interpret the published real-world evidence comparing sequential treatment for mRCC.<h4>Methods</h4>A search was conducted in Medline and Embase (2009-2013), and conference proceedings from American Society of Clinical Oncology (ASCO), ASCO Genitourinary Cancers Symposium (ASCO-GU), and European Society for Medical Oncology (ESMO) (2011-2013). We systematically reviewed observational studies comparing second-line mRCC treatment with mammalian target of rapamycin inhibitors (mTORi) versus vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI). Studies were evaluated for 1) use of a retrospective cohort design after initiation of second-line therapy, 2) adjustment for patient characteristics, and 3) use of data from multiple centers. Meta-analyses were conducted for comparisons of overall survival (OS) and progression-free survival (PFS).<h4>Results</h4>Ten studies reported OS and exhibited significant heterogeneity in estimated second-line treatment effects (I2 = 68%; P = 0.001). Four of these were adjusted, multicenter, retrospective cohort studies, and these showed no evidence of heterogeneity (I2 = 0%; P = 0.61) and a significant association between second-line mTORi (>75% everolimus) and longer OS compared to VEGF TKI (>60% sorafenib) (HR = 0.82, 95% CI: 0.68 to 0.98) in a meta-analysis. Seven studies comparing PFS showed significant heterogeneity overall and among the adjusted, multicenter, retrospective cohort studies. Real-world observational data for axitinib outcomes was limited at the time of this study.<h4>Conclusions</h4>Real-world studies employed different designs and reported heterogeneous results comparing the effectiveness of second-line mTORi and VEGF TKI in the treatment of mRCC. Within the subset of adjusted, multicenter observational studies, second-line use of mTORi was associated with significantly prolonged survival compared with second-line use of VEGF TKI. |
| format | Article |
| id | doaj-art-653ddbb748d94f379317be4d963bb746 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj-art-653ddbb748d94f379317be4d963bb7462025-08-20T03:09:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01912e11426410.1371/journal.pone.0114264Comparative Effectiveness of Second-Line Targeted Therapies for Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-Analysis of Real-World Observational Studies.Daniel Y HengJames SignorovitchElyse SwallowNanxin LiYichen ZhongPaige QinDaisy Y ZhuoXufang WangJinhee ParkSotirios StergiopoulosChristian Kollmannsberger<h4>Objective</h4>The optimal sequencing of targeted therapies for metastatic renal cell carcinoma (mRCC) is unknown. Observational studies with a variety of designs have reported differing results. The objective of this study is to systematically summarize and interpret the published real-world evidence comparing sequential treatment for mRCC.<h4>Methods</h4>A search was conducted in Medline and Embase (2009-2013), and conference proceedings from American Society of Clinical Oncology (ASCO), ASCO Genitourinary Cancers Symposium (ASCO-GU), and European Society for Medical Oncology (ESMO) (2011-2013). We systematically reviewed observational studies comparing second-line mRCC treatment with mammalian target of rapamycin inhibitors (mTORi) versus vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI). Studies were evaluated for 1) use of a retrospective cohort design after initiation of second-line therapy, 2) adjustment for patient characteristics, and 3) use of data from multiple centers. Meta-analyses were conducted for comparisons of overall survival (OS) and progression-free survival (PFS).<h4>Results</h4>Ten studies reported OS and exhibited significant heterogeneity in estimated second-line treatment effects (I2 = 68%; P = 0.001). Four of these were adjusted, multicenter, retrospective cohort studies, and these showed no evidence of heterogeneity (I2 = 0%; P = 0.61) and a significant association between second-line mTORi (>75% everolimus) and longer OS compared to VEGF TKI (>60% sorafenib) (HR = 0.82, 95% CI: 0.68 to 0.98) in a meta-analysis. Seven studies comparing PFS showed significant heterogeneity overall and among the adjusted, multicenter, retrospective cohort studies. Real-world observational data for axitinib outcomes was limited at the time of this study.<h4>Conclusions</h4>Real-world studies employed different designs and reported heterogeneous results comparing the effectiveness of second-line mTORi and VEGF TKI in the treatment of mRCC. Within the subset of adjusted, multicenter observational studies, second-line use of mTORi was associated with significantly prolonged survival compared with second-line use of VEGF TKI.https://doi.org/10.1371/journal.pone.0114264 |
| spellingShingle | Daniel Y Heng James Signorovitch Elyse Swallow Nanxin Li Yichen Zhong Paige Qin Daisy Y Zhuo Xufang Wang Jinhee Park Sotirios Stergiopoulos Christian Kollmannsberger Comparative Effectiveness of Second-Line Targeted Therapies for Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-Analysis of Real-World Observational Studies. PLoS ONE |
| title | Comparative Effectiveness of Second-Line Targeted Therapies for Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-Analysis of Real-World Observational Studies. |
| title_full | Comparative Effectiveness of Second-Line Targeted Therapies for Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-Analysis of Real-World Observational Studies. |
| title_fullStr | Comparative Effectiveness of Second-Line Targeted Therapies for Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-Analysis of Real-World Observational Studies. |
| title_full_unstemmed | Comparative Effectiveness of Second-Line Targeted Therapies for Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-Analysis of Real-World Observational Studies. |
| title_short | Comparative Effectiveness of Second-Line Targeted Therapies for Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-Analysis of Real-World Observational Studies. |
| title_sort | comparative effectiveness of second line targeted therapies for metastatic renal cell carcinoma a systematic review and meta analysis of real world observational studies |
| url | https://doi.org/10.1371/journal.pone.0114264 |
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