Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 May;10(5):2091-2107.
doi: 10.21037/tcr-20-3354.

Effectiveness and safety of combined therapy versus monotherapy based on immune checkpoint inhibitors and/or targeted drugs as salvage treatment for advanced urothelial carcinoma: a systematic review and meta-analysis

Lichao Wei #  1 , Liang Gao #  1 , Zili Hu  1 , Chuan Liu  1
Affiliations

Effectiveness and safety of combined therapy versus monotherapy based on immune checkpoint inhibitors and/or targeted drugs as salvage treatment for advanced urothelial carcinoma: a systematic review and meta-analysis

Lichao Wei et al. Transl Cancer Res. 2021 May.

Abstract

Background: The standard salvage regimen for the patients with advanced urothelial carcinoma (UC) is uncertain, although lots of novel agents are recommended, including immune checkpoint inhibitors (ICIs) and targeted drugs (TDs). We aimed to compare the effectiveness and safety of combined therapy of novel agents (CNA) and monotherapy of novel agents (MNA) as salvage therapy for advanced UC.

Methods: Studies exploring CNA and/or MNA for advanced UC in second-line setting were searched from PubMed, Embase, Cochrane Library, and Web of Science. The data of objective response rate (ORR), disease control rate (DCR), median progression-free survival (PFS), median overall survival (OS), and grade 3-4 adverse effects rate (grade 3-4 AEs%) were pooled for analyses. Cochrane risk of bias tool was applied for the quality judgment of randomized controlled studies (RCTs).

Results: Forty-one arms from 37 studies including 4,691 patients were included. Significant differences were presented in pooled ORR (22.9% versus 12.2%, OR =1.88, P<0.001) and DCR (62.7% versus 37.5%, OR =2.53, P<0.001) between CNA and MNA groups. The pooled median PFS was 3.66 months in CNA group versus 2.16 months in MNA group (WMD =1.50, P=0.028). No significant difference in pooled median OS was found between two groups (7.93 versus 7.50 months, WMD =0.43, P=0.449). 63.7% versus 25.4% of pooled grade 3-4 AEs% could be seen in CNA and MNA groups (OR =3.52, P<0.001). Additionally, the pooled results of PFS-6m and OS-6m in CNA group demonstrated significant advantages over MNA group (31.5% versus 28.7%, OR =1.31, P=0.049; 66.0% versus 56.7%, OR =1.34, P=0.029, respectively). In the subgroup analysis of CNA, use of ICIs, the positive expression of PD-L1 and ECOG-PS =0 were significantly associated with superior clinical outcomes (P<0.05).

Discussion: For advanced UC patients after first line agents, CNA had potential benefits than MNA in terms of ORR, DCR, median PFS, PFS-6m and OS-6m. However, CNA was associated with a significantly higher grade 3-4 AEs%. Furthermore, potential advantages were presented in CNA patients with ICIs usage, positive PD-L1 expression and ECOG-PS =0.

Keywords: Urothelial carcinoma (UC); combined therapy; monotherapy; novel agents; salvage therapy.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr-20-3354). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
The flow chart of study identification.
Figure 2
Figure 2
Forest plots of response outcomes of CNA and MNA. (A) Pooled ORR of CNA. (B) Pooled ORR of MNA. (C) Pooled DCR of CNA. (D) Pooled DCR of MNA. CNA, combined therapy of novel agents; MNA, monotherapy of novel agents; ORR, objective response rate; DCR, disease control rate.
Figure 3
Figure 3
Forest plots of survival outcomes of CNA and MNA. (A) Pooled median PFS of CNA. (B) Pooled median PFS of MNA. (C) Pooled median OS of CNA. (D) Pooled median OS of MNA. CNA, combined therapy of novel agents; MNA, monotherapy of novel agents; PFS, progression-free survival; OS, overall survival.
Figure 4
Figure 4
Forest plots of toxicity of CNA and MNA. (A) Pooled grade 3-4 AEs% of CNA. (B) Pooled grade 3-4 AEs% of MNA. CNA, combined therapy of novel agents; MNA, monotherapy of novel agents; grade 3-4 AEs%, grade 3 or 4 adverse events rate.
Figure 5
Figure 5
Forest plots of the subgroup analyses in CNA group. (A) ORR of PD-L1(+) vs. PD-L1(-). (B) DCR of PD-L1(+) vs. PD-L1(-). (C) ORR of ECOG-PS =0 vs. ECOG-PS ≥1. CNA, combined therapy of novel agents; ORR, objective response rate; DCR, disease control rate; PD-L1, programmed death-ligand 1; ECOG-PS, Eastern Cooperative Oncology Group Performance Status.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. von der Maase H, Hansen SW, Roberts JT, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol 2000;18:3068-77. 10.1200/JCO.2000.18.17.3068 - DOI - PubMed
    1. Sternberg CN, de Mulder P, Schornagel JH, et al. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Cancer 2006;42:50-4. 10.1016/j.ejca.2005.08.032 - DOI - PubMed
    1. Bellmunt J, de Wit R, Vaughn DJ, et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med 2017;376:1015-26. 10.1056/NEJMoa1613683 - DOI - PMC - PubMed
    1. Necchi A, Mariani L, Zaffaroni N, et al. Pazopanib in Advanced and Platinum-Resistant Urothelial Cancer: An Open-Label, Single Group, Phase 2 Trial. Lancet Oncol 2012;13:810-6. 10.1016/S1470-2045(12)70294-2 - DOI - PubMed
    1. Sharma P, Siefker-Radtke A, de Braud F, et al. Nivolumab Alone and With Ipilimumab in Previously Treated Metastatic Urothelial Carcinoma: CheckMate 032 Nivolumab 1 mg/kg Plus Ipilimumab 3 mg/kg Expansion Cohort Results. J Clin Oncol 2019;37:1608-16. 10.1200/JCO.19.00538 - DOI - PMC - PubMed