Systematic Literature Review (SLR) and Network Meta-Analysis (NMA) of First-Line Therapies (1L) for Locally Advanced/Metastatic Urothelial Carcinoma (la/mUC)
To compare efficacy outcomes for all approved and investigational first-line (1L) treatment regimens for locally advanced or metastatic urothelial carcinoma (la/mUC) with standard of care (SOC), a network meta-analysis (NMA) was conducted. A systematic literature review (SLR) identified phase 2 and...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Current Oncology |
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| Online Access: | https://www.mdpi.com/1718-7729/30/4/277 |
| _version_ | 1797605858618638336 |
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| author | Lisa Bloudek Phoebe Wright Caroline McKay Christina Louise Derleth Jennifer Susan Lill Enrique Lenero Zsolt Hepp Scott David Ramsey Sean D. Sullivan Beth Devine |
| author_facet | Lisa Bloudek Phoebe Wright Caroline McKay Christina Louise Derleth Jennifer Susan Lill Enrique Lenero Zsolt Hepp Scott David Ramsey Sean D. Sullivan Beth Devine |
| author_sort | Lisa Bloudek |
| collection | DOAJ |
| description | To compare efficacy outcomes for all approved and investigational first-line (1L) treatment regimens for locally advanced or metastatic urothelial carcinoma (la/mUC) with standard of care (SOC), a network meta-analysis (NMA) was conducted. A systematic literature review (SLR) identified phase 2 and 3 randomized trials investigating 1L treatment regimens in la/mUC published January 2001–September 2021. Three networks were formed based on cisplatin (cis) eligibility: cis-eligible/mixed (cis-eligible patients and mixed populations of cis-eligible/ineligible patients), cis-ineligible (strict; exclusively cis-ineligible patients), and cis-ineligible (wide; including studies with investigator’s choice of carbo). Analyses examined comparative efficacy by hazard ratio (HR) for overall survival (OS), and progression-free survival (PFS), and odds ratio (OR) for overall response rate (ORR), with 1L regimens vs. SOC. SOC was gemcitabine + cis (GemCis) or carboplatin (GemCarbo), cis-eligible/mixed network, and GemCarbo cis-ineligible networks. Of 1906 SLR identified citations, 55 trials were selected for data extraction. The NMA comprised 11, 6, and 8 studies in the cis-eligible/mixed, cis-ineligible (strict), cis-ineligible (wide) networks, respectively. In a meta-analysis of SOC control arms, median (95% CI) overall survival (OS) in months varied by network: 13.19 (12.43, 13.95) cis-eligible/mixed, 11.96 (10.43, 13.48) cis-ineligible (wide), and 9.74 (6.71, 12.76) cis-ineligible (strict). Most differences in OS, PFS, and ORR with treatment regimens across treatment networks were not statistically significant compared with SOC. Outcomes with current 1L regimens remain poor, and few significant improvements over SOC have been made, despite inclusion of recent clinical trial data, highlighting an unmet need in the la/mUC patient population. |
| first_indexed | 2024-03-11T05:07:02Z |
| format | Article |
| id | doaj.art-78b13a372e34463d839cddbe2ba03964 |
| institution | Directory Open Access Journal |
| issn | 1198-0052 1718-7729 |
| language | English |
| last_indexed | 2024-03-11T05:07:02Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Oncology |
| spelling | doaj.art-78b13a372e34463d839cddbe2ba039642023-11-17T18:52:29ZengMDPI AGCurrent Oncology1198-00521718-77292023-03-013043637364710.3390/curroncol30040277Systematic Literature Review (SLR) and Network Meta-Analysis (NMA) of First-Line Therapies (1L) for Locally Advanced/Metastatic Urothelial Carcinoma (la/mUC)Lisa Bloudek0Phoebe Wright1Caroline McKay2Christina Louise Derleth3Jennifer Susan Lill4Enrique Lenero5Zsolt Hepp6Scott David Ramsey7Sean D. Sullivan8Beth Devine9Curta Inc., Seattle, WA 98116, USASeagen Inc., Bothell, WA 98021, USAAstellas Pharma Global Development, Inc., Northbrook, IL 60062, USASeagen Inc., Bothell, WA 98021, USASeagen Inc., Bothell, WA 98021, USAAstellas Pharma Global Development, Inc., Northbrook, IL 60062, USASeagen Inc., Bothell, WA 98021, USACurta Inc., Seattle, WA 98116, USACurta Inc., Seattle, WA 98116, USACHOICE Institute, School of Pharmacy, University of Washington, Seattle, WA 98195, USATo compare efficacy outcomes for all approved and investigational first-line (1L) treatment regimens for locally advanced or metastatic urothelial carcinoma (la/mUC) with standard of care (SOC), a network meta-analysis (NMA) was conducted. A systematic literature review (SLR) identified phase 2 and 3 randomized trials investigating 1L treatment regimens in la/mUC published January 2001–September 2021. Three networks were formed based on cisplatin (cis) eligibility: cis-eligible/mixed (cis-eligible patients and mixed populations of cis-eligible/ineligible patients), cis-ineligible (strict; exclusively cis-ineligible patients), and cis-ineligible (wide; including studies with investigator’s choice of carbo). Analyses examined comparative efficacy by hazard ratio (HR) for overall survival (OS), and progression-free survival (PFS), and odds ratio (OR) for overall response rate (ORR), with 1L regimens vs. SOC. SOC was gemcitabine + cis (GemCis) or carboplatin (GemCarbo), cis-eligible/mixed network, and GemCarbo cis-ineligible networks. Of 1906 SLR identified citations, 55 trials were selected for data extraction. The NMA comprised 11, 6, and 8 studies in the cis-eligible/mixed, cis-ineligible (strict), cis-ineligible (wide) networks, respectively. In a meta-analysis of SOC control arms, median (95% CI) overall survival (OS) in months varied by network: 13.19 (12.43, 13.95) cis-eligible/mixed, 11.96 (10.43, 13.48) cis-ineligible (wide), and 9.74 (6.71, 12.76) cis-ineligible (strict). Most differences in OS, PFS, and ORR with treatment regimens across treatment networks were not statistically significant compared with SOC. Outcomes with current 1L regimens remain poor, and few significant improvements over SOC have been made, despite inclusion of recent clinical trial data, highlighting an unmet need in the la/mUC patient population.https://www.mdpi.com/1718-7729/30/4/277bladder cancersystematic literature reviewnetwork meta-analysisstandard of careoncologyoverall survival |
| spellingShingle | Lisa Bloudek Phoebe Wright Caroline McKay Christina Louise Derleth Jennifer Susan Lill Enrique Lenero Zsolt Hepp Scott David Ramsey Sean D. Sullivan Beth Devine Systematic Literature Review (SLR) and Network Meta-Analysis (NMA) of First-Line Therapies (1L) for Locally Advanced/Metastatic Urothelial Carcinoma (la/mUC) Current Oncology bladder cancer systematic literature review network meta-analysis standard of care oncology overall survival |
| title | Systematic Literature Review (SLR) and Network Meta-Analysis (NMA) of First-Line Therapies (1L) for Locally Advanced/Metastatic Urothelial Carcinoma (la/mUC) |
| title_full | Systematic Literature Review (SLR) and Network Meta-Analysis (NMA) of First-Line Therapies (1L) for Locally Advanced/Metastatic Urothelial Carcinoma (la/mUC) |
| title_fullStr | Systematic Literature Review (SLR) and Network Meta-Analysis (NMA) of First-Line Therapies (1L) for Locally Advanced/Metastatic Urothelial Carcinoma (la/mUC) |
| title_full_unstemmed | Systematic Literature Review (SLR) and Network Meta-Analysis (NMA) of First-Line Therapies (1L) for Locally Advanced/Metastatic Urothelial Carcinoma (la/mUC) |
| title_short | Systematic Literature Review (SLR) and Network Meta-Analysis (NMA) of First-Line Therapies (1L) for Locally Advanced/Metastatic Urothelial Carcinoma (la/mUC) |
| title_sort | systematic literature review slr and network meta analysis nma of first line therapies 1l for locally advanced metastatic urothelial carcinoma la muc |
| topic | bladder cancer systematic literature review network meta-analysis standard of care oncology overall survival |
| url | https://www.mdpi.com/1718-7729/30/4/277 |
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