Immunotherapy versus chemotherapy as first-line treatment for advanced urothelial cancer: A systematic review and meta-analysis

Alberto Martini; Daniele Raggi; Giuseppe Fallara; Luigi Nocera; Julianne G Schultz; Federico Belladelli; Laura Marandino; Andrea Salonia; Alberto Briganti; Francesco Montorsi; Thomas Powles; Andrea Necchi

doi:10.1016/j.ctrv.2022.102360

Immunotherapy versus chemotherapy as first-line treatment for advanced urothelial cancer: A systematic review and meta-analysis

Cancer Treat Rev. 2022 Mar:104:102360. doi: 10.1016/j.ctrv.2022.102360. Epub 2022 Feb 10.

Authors

Affiliations

¹ Division of Experimental Oncology/Unit of Urology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: a.martini.md@gmail.com.
² Division of Experimental Oncology/Unit of Urology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
³ National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
⁴ Service of Medical Oncology, Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland.
⁵ Division of Experimental Oncology/Unit of Urology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
⁶ Barts Cancer Institute, Queen Mary University of London, UK.

PMID: 35176685
DOI: 10.1016/j.ctrv.2022.102360

Abstract

Background: Pembrolizumab and atezolizumab have recently been approved for the first-line treatment of patients with advanced urothelial carcinoma (aUC) who are not eligible for cisplatin-based chemotherapy and whose tumors have high PD-L1 expression; however, the use of these immunotherapeutic agents relative to standard of care chemotherapy has ongoing concerns. The aim of this present study is to compare the effectiveness of single-agent immune-oncology (IO) compounds versus platinum-based chemotherapy in the first-line setting of aUC.

Methods: A comprehensive search for phase III trials on IO versus chemotherapy was conducted in PubMed, EMBASE, Web of Science, and Scopus databases from 01/2016 to 05/2021. An algorithm to obtain survival data from published Kaplan-Meier curves was used to reconstruct overall survival (OS) data. After demonstrating violation of the proportional hazard assumption, we used the difference in restricted mean survival time (ΔRMST) to compare OS.

Results: OS data from 2,068 individuals from 3 phase III trials investigating the role of IO vs chemotherapy were reconciled. Overall, patients receiving IO [n = 1,013 (49%)] or chemotherapy [n = 1,055 (51%)] had similar OS with a 24-month ΔRMST of -0.4 (95% CI: -1.1, 0.4; p = 0.2) months. In the cisplatin-ineligible population, patients receiving IO [n = 509 (49%)] or chemotherapy [n = 530 (51%)] had similar OS with a 24-month ΔRMST of 0.1 (95% CI: -0.9, 1.2; p = 0.7) months. In the cisplatin-ineligible population with PD-L1-high tumors, patients receiving IO [n = 226 (50%)] or chemotherapy [n = 226 (50%)] had similar OS with a 24-month ΔRMST of 1.1 (95% CI: -0.5, 2.7; p = 0.1) months.

Conclusion: We found no OS benefit for patients treated with first-line immune checkpoint inhibition compared to chemotherapy among the overall population, cisplatin-ineligible patients, and PD-L1-high patients.

Keywords: Advanced urothelial carcinoma; Carboplatin chemotherapy; Meta-analysis; Overall survival; Systemic therapy.

Publication types

Meta-Analysis
Review
Systematic Review

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Carcinoma, Transitional Cell* / drug therapy
Cisplatin / therapeutic use
Humans
Immunotherapy
Urinary Bladder Neoplasms* / drug therapy

Substances

Cisplatin