Novel combination therapy for platinum-eligible patients with locally advanced or metastatic urothelial carcinoma: a systematic review and network meta-analysis
Abstract Recent phase 3 randomized controlled trials (RCTs) demonstrate the promising impact of immune checkpoint inhibitor (ICI)-based combination therapies on locally advanced or metastatic urothelial carcinoma (UC). However, comparative data on the efficacy and toxicity of different ICI-based com...
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Springer
2025-02-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-024-03910-3 |
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| author | Takafumi Yanagisawa Keiichiro Mori Akihiro Matsukawa Tatsushi Kawada Satoshi Katayama Ekaterina Laukhtina Pawel Rajwa Fahad Quhal Benjamin Pradere Wataru Fukuokaya Kosuke Iwatani Renate Pichler Jeremy Yuen-Chun Teoh Marco Moschini Wojciech Krajewski Jun Miki Shahrokh F. Shariat Takahiro Kimura European Association of Urology–Young Academic Urologists Urothelial Carcinoma Working Group (EAU-YAU) |
| author_facet | Takafumi Yanagisawa Keiichiro Mori Akihiro Matsukawa Tatsushi Kawada Satoshi Katayama Ekaterina Laukhtina Pawel Rajwa Fahad Quhal Benjamin Pradere Wataru Fukuokaya Kosuke Iwatani Renate Pichler Jeremy Yuen-Chun Teoh Marco Moschini Wojciech Krajewski Jun Miki Shahrokh F. Shariat Takahiro Kimura European Association of Urology–Young Academic Urologists Urothelial Carcinoma Working Group (EAU-YAU) |
| author_sort | Takafumi Yanagisawa |
| collection | DOAJ |
| description | Abstract Recent phase 3 randomized controlled trials (RCTs) demonstrate the promising impact of immune checkpoint inhibitor (ICI)-based combination therapies on locally advanced or metastatic urothelial carcinoma (UC). However, comparative data on the efficacy and toxicity of different ICI-based combinations are lacking. This study aims to compare the efficacy of first-line ICI-based combination therapies for locally advanced or metastatic UC using phase 3 RCT data. In November 2023, three databases were searched for RCTs evaluating oncological outcomes in patients with locally advanced or metastatic UC who were treated with first-line ICI-based combination therapies. Network meta-analysis (NMA) was conducted to compare outcomes, including overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), complete response rates (CRRs), and treatment-related adverse events (TRAEs). Subgroup analyses were based on PD-L1 status and cisplatin eligibility. The NMA included five RCTs. Enfortumab vedotin (EV) + pembrolizumab ranked the highest for improving OS (100%), PFS (100%), ORR (96%), and CRR (96%), followed by nivolumab + chemotherapy. EV + pembrolizumab combination superiority held across PD-L1 status and cisplatin eligibility. In patients who are cisplatin-eligible, EV + pembrolizumab significantly improved OS (HR: 0.68, 95%CI 0.47–0.99) and PFS (HR: 0.67, 95%CI 0.49–0.92) compared to nivolumab + chemotherapy. Durvalumab + tremelimumab was the safest combination for severe TRAEs, and EV + pembrolizumab ranked second. Our analyses support EV + pembrolizumab combination as a first-line treatment for locally advanced or metastatic UC. Thus, EV + pembrolizumab may become a guideline-changing standard treatment. |
| format | Article |
| id | doaj-art-724f2b007c2a4d2f9e8664134de72f1d |
| institution | Kabale University |
| issn | 1432-0851 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-724f2b007c2a4d2f9e8664134de72f1d2025-02-02T12:26:29ZengSpringerCancer Immunology, Immunotherapy1432-08512025-02-0174311410.1007/s00262-024-03910-3Novel combination therapy for platinum-eligible patients with locally advanced or metastatic urothelial carcinoma: a systematic review and network meta-analysisTakafumi Yanagisawa0Keiichiro Mori1Akihiro Matsukawa2Tatsushi Kawada3Satoshi Katayama4Ekaterina Laukhtina5Pawel Rajwa6Fahad Quhal7Benjamin Pradere8Wataru Fukuokaya9Kosuke Iwatani10Renate Pichler11Jeremy Yuen-Chun Teoh12Marco Moschini13Wojciech Krajewski14Jun Miki15Shahrokh F. Shariat16Takahiro Kimura17European Association of Urology–Young Academic Urologists Urothelial Carcinoma Working Group (EAU-YAU)Department of Urology, Comprehensive Cancer Center, Medical University of ViennaDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaDepartment of Urology, The Jikei University School of MedicineDepartment of Urology, The Jikei University School of MedicineDepartment of Urology, Comprehensive Cancer Center Innsbruck (CCCI), Medical University of InnsbruckS.H. Ho Urology Centre, Department of Surgery, The Chinese University of Hong KongDepartment of Urology, San Raffaele Hospital and Scientific InstituteDepartment of Minimally Invasive and Robotic Urology, Wrocław Medical UniversityDepartment of Urology, The Jikei University School of MedicineDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaDepartment of Urology, The Jikei University School of MedicineAbstract Recent phase 3 randomized controlled trials (RCTs) demonstrate the promising impact of immune checkpoint inhibitor (ICI)-based combination therapies on locally advanced or metastatic urothelial carcinoma (UC). However, comparative data on the efficacy and toxicity of different ICI-based combinations are lacking. This study aims to compare the efficacy of first-line ICI-based combination therapies for locally advanced or metastatic UC using phase 3 RCT data. In November 2023, three databases were searched for RCTs evaluating oncological outcomes in patients with locally advanced or metastatic UC who were treated with first-line ICI-based combination therapies. Network meta-analysis (NMA) was conducted to compare outcomes, including overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), complete response rates (CRRs), and treatment-related adverse events (TRAEs). Subgroup analyses were based on PD-L1 status and cisplatin eligibility. The NMA included five RCTs. Enfortumab vedotin (EV) + pembrolizumab ranked the highest for improving OS (100%), PFS (100%), ORR (96%), and CRR (96%), followed by nivolumab + chemotherapy. EV + pembrolizumab combination superiority held across PD-L1 status and cisplatin eligibility. In patients who are cisplatin-eligible, EV + pembrolizumab significantly improved OS (HR: 0.68, 95%CI 0.47–0.99) and PFS (HR: 0.67, 95%CI 0.49–0.92) compared to nivolumab + chemotherapy. Durvalumab + tremelimumab was the safest combination for severe TRAEs, and EV + pembrolizumab ranked second. Our analyses support EV + pembrolizumab combination as a first-line treatment for locally advanced or metastatic UC. Thus, EV + pembrolizumab may become a guideline-changing standard treatment.https://doi.org/10.1007/s00262-024-03910-3ChemotherapyEnfortumab vedotinImmune checkpoint inhibitorsMetastasisUrothelial carcinoma |
| spellingShingle | Takafumi Yanagisawa Keiichiro Mori Akihiro Matsukawa Tatsushi Kawada Satoshi Katayama Ekaterina Laukhtina Pawel Rajwa Fahad Quhal Benjamin Pradere Wataru Fukuokaya Kosuke Iwatani Renate Pichler Jeremy Yuen-Chun Teoh Marco Moschini Wojciech Krajewski Jun Miki Shahrokh F. Shariat Takahiro Kimura European Association of Urology–Young Academic Urologists Urothelial Carcinoma Working Group (EAU-YAU) Novel combination therapy for platinum-eligible patients with locally advanced or metastatic urothelial carcinoma: a systematic review and network meta-analysis Cancer Immunology, Immunotherapy Chemotherapy Enfortumab vedotin Immune checkpoint inhibitors Metastasis Urothelial carcinoma |
| title | Novel combination therapy for platinum-eligible patients with locally advanced or metastatic urothelial carcinoma: a systematic review and network meta-analysis |
| title_full | Novel combination therapy for platinum-eligible patients with locally advanced or metastatic urothelial carcinoma: a systematic review and network meta-analysis |
| title_fullStr | Novel combination therapy for platinum-eligible patients with locally advanced or metastatic urothelial carcinoma: a systematic review and network meta-analysis |
| title_full_unstemmed | Novel combination therapy for platinum-eligible patients with locally advanced or metastatic urothelial carcinoma: a systematic review and network meta-analysis |
| title_short | Novel combination therapy for platinum-eligible patients with locally advanced or metastatic urothelial carcinoma: a systematic review and network meta-analysis |
| title_sort | novel combination therapy for platinum eligible patients with locally advanced or metastatic urothelial carcinoma a systematic review and network meta analysis |
| topic | Chemotherapy Enfortumab vedotin Immune checkpoint inhibitors Metastasis Urothelial carcinoma |
| url | https://doi.org/10.1007/s00262-024-03910-3 |
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