TY - JOUR
T1 - Reassessment of the Efficacy of Carboplatin for Metastatic Urothelial Carcinoma in the Era of Immunotherapy
T2 - A Systematic Review and Meta-analysis
AU - European Association of Urology–Young Academic Urologists Urothelial Carcinoma Working Group (EAU-YAU)
AU - Mori, Keiichiro
AU - Schuettfort, Victor M.
AU - Yanagisawa, Takafumi
AU - Katayama, Satoshi
AU - Pradere, Benjamin
AU - Laukhtina, Ekaterina
AU - Rajwa, Pawel
AU - Mostafaei, Hadi
AU - Sari Motlagh, Reza
AU - Quhal, Fahad
AU - Moschini, Marco
AU - Soria, Francesco
AU - Teoh, Jeremy Y.C.
AU - D'Andrea, David
AU - Abufaraj, Mohammad
AU - Albisinni, Simone
AU - Krajewski, Wojciech
AU - Egawa, Shin
AU - Karakiewicz, Pierre I.
AU - Rink, Michael
AU - Shariat, Shahrokh F.
N1 - Funding Information:
Funding/Support and role of the sponsor: Victor M. Schuettfort, Ekaterina Laukhtina, and Pawel Rajwa are supported by the EUSP Scholarship of the European Association of Urology. Keiichiro Mori is supported by The Uehara Memorial Foundation.
Publisher Copyright:
© 2022 The Author(s)
PY - 2022
Y1 - 2022
N2 - Context: Platinum-based combination chemotherapy is the standard treatment for advanced or metastatic urothelial carcinoma (AMUC). However, data comparing the efficacy of different platinum agents are limited. Objective: This review aimed to assess the efficacy of carboplatin as a first-line treatment for AMUC using phase 3 randomized trial data. Evidence acquisition: Multiple databases were searched for articles published until August 2021. Studies that compared overall survival (OS), complete response (CR), and objective response rates (ORRs) in chemotherapy-eligible patients with AMUC were deemed eligible. Evidence synthesis: Four studies were included. Compared with immune checkpoint inhibitor (ICI) monotherapy, neither cisplatin- nor carboplatin-based chemotherapy was associated with significant OS (hazard ratio [HR]: 0.97, 95% confidence interval [CI]: 0.85–1.11, p = 0.64 and HR: 0.90, 95% CI: 0.78–1.04, p = 0.16, respectively) and CR (odds ratio [OR]: 1.16, 95% CI: 0.70–1.92, p = 0.57 and OR: 0.89, 95% CI: 0.52–1.53, p = 0.67, respectively benefits, while both were associated with a favorable ORR (OR: 0.54, 95% CI: 0.40–0.74, p < 0.001 and OR: 0.58, 95% CI: 0.42–0.80, p < 0.001, respectively). A network meta-analysis (NMA)-based indirect comparison between carboplatin and cisplatin revealed that while cisplatin was slightly better than carboplatin in terms of OS, CR, and ORR, no significant difference was noted. Conclusions: Cisplatin- and carboplatin-based chemotherapies offer similar OS/CR benefits to ICI monotherapy and elicit a greater ORR than ICI monotherapy. Moreover, our NMA demonstrated that both cisplatin- and carboplatin-based chemotherapy have a similar efficacy in terms of OS, CR, and ORR. Given that carboplatin-based chemotherapy is shown to be more effective in contemporary series than in historical controls, it is strongly recommended that carboplatin be re-examined for its value in the era of ICIs and beyond. Patient summary: Cisplatin- as well as carboplatin-based chemotherapy is as effective as immune checkpoint inhibitors in terms of survival and eliciting a positive response. It is currently believed that cisplatin provides greater benefits than carboplatin; this requires re-evaluation.
AB - Context: Platinum-based combination chemotherapy is the standard treatment for advanced or metastatic urothelial carcinoma (AMUC). However, data comparing the efficacy of different platinum agents are limited. Objective: This review aimed to assess the efficacy of carboplatin as a first-line treatment for AMUC using phase 3 randomized trial data. Evidence acquisition: Multiple databases were searched for articles published until August 2021. Studies that compared overall survival (OS), complete response (CR), and objective response rates (ORRs) in chemotherapy-eligible patients with AMUC were deemed eligible. Evidence synthesis: Four studies were included. Compared with immune checkpoint inhibitor (ICI) monotherapy, neither cisplatin- nor carboplatin-based chemotherapy was associated with significant OS (hazard ratio [HR]: 0.97, 95% confidence interval [CI]: 0.85–1.11, p = 0.64 and HR: 0.90, 95% CI: 0.78–1.04, p = 0.16, respectively) and CR (odds ratio [OR]: 1.16, 95% CI: 0.70–1.92, p = 0.57 and OR: 0.89, 95% CI: 0.52–1.53, p = 0.67, respectively benefits, while both were associated with a favorable ORR (OR: 0.54, 95% CI: 0.40–0.74, p < 0.001 and OR: 0.58, 95% CI: 0.42–0.80, p < 0.001, respectively). A network meta-analysis (NMA)-based indirect comparison between carboplatin and cisplatin revealed that while cisplatin was slightly better than carboplatin in terms of OS, CR, and ORR, no significant difference was noted. Conclusions: Cisplatin- and carboplatin-based chemotherapies offer similar OS/CR benefits to ICI monotherapy and elicit a greater ORR than ICI monotherapy. Moreover, our NMA demonstrated that both cisplatin- and carboplatin-based chemotherapy have a similar efficacy in terms of OS, CR, and ORR. Given that carboplatin-based chemotherapy is shown to be more effective in contemporary series than in historical controls, it is strongly recommended that carboplatin be re-examined for its value in the era of ICIs and beyond. Patient summary: Cisplatin- as well as carboplatin-based chemotherapy is as effective as immune checkpoint inhibitors in terms of survival and eliciting a positive response. It is currently believed that cisplatin provides greater benefits than carboplatin; this requires re-evaluation.
KW - Carboplatin
KW - Cisplatin
KW - Immune checkpoint inhibitors
KW - Platinum-based chemotherapy
KW - Urothelial carcinoma
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U2 - 10.1016/j.euf.2022.02.007
DO - 10.1016/j.euf.2022.02.007
M3 - Review article
C2 - 35279408
AN - SCOPUS:85126007954
SN - 2405-4569
JO - European Urology Focus
JF - European Urology Focus
ER -