Reassessment of the Efficacy of Carboplatin for Metastatic Urothelial Carcinoma in the Era of Immunotherapy: A Systematic Review and Meta-analysis

TY - JOUR

T1 - Reassessment of the Efficacy of Carboplatin for Metastatic Urothelial Carcinoma in the Era of Immunotherapy: A Systematic Review and Meta-analysis

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

AU - European Association of Urology – Young Academic Urologists (EAU-YAU), Urothelial Carcinoma Working Group

N1 - Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.

PY - 2022/11

Y1 - 2022/11

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 - Humans

KW - Carboplatin/therapeutic use

KW - Carcinoma, Transitional Cell/drug therapy

KW - Urinary Bladder Neoplasms

U2 - 10.1016/j.euf.2022.02.007

DO - 10.1016/j.euf.2022.02.007

M3 - SCORING: Review article

C2 - 35279408

VL - 8

SP - 1687

EP - 1695

JO - EUR UROL FOCUS

JF - EUR UROL FOCUS

SN - 2405-4569

IS - 6

ER -