Optimal first-line treatment for platinum-eligible metastatic urothelial carcinoma: Comparison of chemo-immunotherapy, immunotherapy, and chemotherapy— A systematic review and meta-analysis

Li, Haifeng; Ni, Mengqian; Xue, Cong; Li, Lü; Huang, Riqing; Yang, Wei; Hu, Anqi; An, Xin; Shi, Yanxia

doi:10.1016/j.clim.2022.108927

Cited by 6 publications

(4 citation statements)

References 19 publications

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“…Although the difference in OS was not statistically significant (p = 0.204), which might be due to a shortage of OS time, certain survival benefits were still observed in the immunochemotherapy group in terms of survival time and survival curve. Our results are generally consistent with previous studies 20,[25][26][27][28] and support PD-1/PD-L1 inhibitors plus platinum-based chemotherapy as a promising treatment to improve efficacy. Clinical studies KEYNOTE-361 and IMvigor130 both compared the efficacy of first-line chemotherapy with immunochemotherapy in patients with Although the conclusions of these two studies were not completely identical, and the efficacy advantage of the combination therapy group was not as significant as in non-small-cell lung cancer, prolonged PFS and OS were observed, which was similar to the results of our study.…”

Section: Discussionsupporting

confidence: 92%

“…Although the difference in OS was not statistically significant ( p = 0.204), which might be due to a shortage of OS time, certain survival benefits were still observed in the immunochemotherapy group in terms of survival time and survival curve. Our results are generally consistent with previous studies 20 , 25 , 26 , 27 , 28 and support PD‐1/PD‐L1 inhibitors plus platinum‐based chemotherapy as a promising treatment to improve efficacy. Clinical studies KEYNOTE‐361 and IMvigor130 both compared the efficacy of first‐line chemotherapy with immunochemotherapy in patients with advanced UC.…”

Section: Discussionsupporting

confidence: 92%

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The efficacy and safety of chemotherapy with or without anti‐PD‐1 for the first‐line treatment of advanced urothelial carcinoma

Han,

Wu,

Chen

et al. 2023

Cancer Medicine

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ObjectiveTo compare the efficacy and safety of first‐line anti‐PD‐1 combined with chemotherapy versus chemotherapy alone in patients with advanced urothelial carcinoma (UC).MethodPatients with advanced UC who received first‐line treatment of chemotherapy (n = 51, gemcitabine/paclitaxel [albumin‐bound] combined with platinum) or immunochemotherapy (n = 50, PD‐1 inhibitors plus chemotherapy) were enrolled. The efficacy and safety were analyzed between the two groups.ResultsThis study included data from 101 patients, including 51 patients in the chemotherapy group and 50 patients in the immunochemotherapy group. The median progression‐free survival of the immunochemotherapy group was significantly longer than that of the chemotherapy group (11.5 vs. 7.17 m, HR = 0.56, p = 0.009). The two groups' overall survival showed no significant difference (20.3 vs. 17.8 m, p = 0.204). The objective response rates and the disease control rates of the two groups were 38.0% versus 49.0% (p = 0.26) and 88.0% versus 80.4% (p = 0.29). The incidence of adverse reactions (AEs) in the immunochemotherapy group and chemotherapy group were 90.0% and 84.3% (p = 0.394), respectively, and the incidence of Grade III–IV AEs were 32.0% and 35.3% (p = 0.726), respectively.ConclusionIn the first‐line treatment of patients with advanced UC, anti‐PD‐1 therapy combined with chemotherapy might have better efficacy than chemotherapy alone, and AEs are similar between the two groups.

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Section: Discussionsupporting

confidence: 92%

“…Although the difference in OS was not statistically significant ( p = 0.204), which might be due to a shortage of OS time, certain survival benefits were still observed in the immunochemotherapy group in terms of survival time and survival curve. Our results are generally consistent with previous studies 20 , 25 , 26 , 27 , 28 and support PD‐1/PD‐L1 inhibitors plus platinum‐based chemotherapy as a promising treatment to improve efficacy. Clinical studies KEYNOTE‐361 and IMvigor130 both compared the efficacy of first‐line chemotherapy with immunochemotherapy in patients with advanced UC.…”

Section: Discussionsupporting

confidence: 92%

The efficacy and safety of chemotherapy with or without anti‐PD‐1 for the first‐line treatment of advanced urothelial carcinoma

Han,

Wu,

Chen

et al. 2023

Cancer Medicine

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“…We provide aggregated data from five RCTs on the efficacy of PD-1/PD-L1 inhibitors in the ≥5% PD-L1 expression status threshold, determining whether survival rate or response rate results show no statistically significant difference in efficacy when compared with chemotherapy alone. Another meta-analysis has looked at the efficacy and/or safety of PD-(L)1-containing therapies based on the patient's PD-L1 status [33,41,42].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Programmed Death-1/Programmed Death-Ligand 1 Inhibitor for Metastatic Urothelial Carcinoma: A Systematic Review and Meta-Analysis

Liao,

Wang,

Peng

2023

Current Oncology

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Objective: The purpose of this study was to evaluate the efficacy and safety of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors for the treatment of metastatic urothelial carcinoma (mUC). Methods: A literature search was conducted of PubMed, EMBASE, and the Cochrane Library and was limited to the English literature. Randomized controlled trials (RCTs) published up to July 2022 were considered for inclusion. The outcomes were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and grade ≥ 3 treatment-related AEs (TRAE). Subgroup analysis was performed based on the PD-L1 expression status, and the differences between first- and second-line PD-1/PD-L1 inhibitors were estimated. Results: We included five RCTs comprising 3584 patients in the analysis. Compared with chemotherapy alone, the use of PD-1/PD-L1 inhibitors as monotherapy did not significantly prolong OS [hazard ratios (HR), 0.90; 95% CI, 0.81–1.00] or PFS (HR, 1.12; 95% CI, 0.95–1.32). However, the PD-1/PD-L1 inhibitor combined with chemotherapy significantly improved both OS (HR, 0.85; 95% CI, 0.74–0.96) and PFS (HR, 0.80; 95% CI, 0.71–0.90). Additionally, subgroup analysis showed that in mUC with PD-L1 expression ≥ 5%, treatment with the PD-1/PD-L1 inhibitor alone did not reduce the risk of death. Safety analysis showed that the PD-1/PD-L1 inhibitor alone did not significantly increase the incidence rates of grade ≥ 3 TRAEs. Conclusions: The results show that use of the PD-1/PD-L1 inhibitor alone as first-line treatment is similar to chemotherapy in terms of both survival and response rates. However, the PD-1/PD-L1 inhibitor plus chemotherapy has a significant benefit in terms of PFS or OS. Nonetheless, more RCTs are warranted to evaluate efficiency and safety in the combination regimen of chemotherapy and PD-1/PD-L1 inhibitors.

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“…Currently, cisplatin-based chemotherapy is the standard chemotherapy regimen for patients with advanced muscle-invasive bladder cancer (MIBC) [ 1 – 3 ]. However, even immune checkpoint inhibitors, as the palliative first-line setting, combined with cisplatin do not improve survival [ 4 – 6 ]. Moreover, although avelumab is approved to be administered as a maintenance treatment following platinum-based chemotherapy, the survival benefit is approximately six months, while a long-term survival benefit is observed in only a limited number of patients [ 7 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

New insights into ATR inhibition in muscle invasive bladder cancer: The role of apolipoprotein B mRNA editing catalytic subunit 3B

KIM,

CHO,

HONG

et al. 2024

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Background Apolipoprotein B mRNA editing catalytic polypeptide (APOBEC), an endogenous mutator, induces DNA damage and activates the ataxia telangiectasia and Rad3-related (ATR)-checkpoint kinase 1 (Chk1) pathway. Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer (MIBC), it has a poor survival rate. Therefore, this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B (APOBEC3B) expressing MIBC. Methods Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC. The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis. Western blot analysis was performed to confirm differences in phosphorylated Chk1 (pChk1) expression according to the APOBEC3B expression. Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin. Conclusion There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC. Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels. Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression. Compared to cisplatin single treatment, combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression. Conclusion: Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition. This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

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Optimal first-line treatment for platinum-eligible metastatic urothelial carcinoma: Comparison of chemo-immunotherapy, immunotherapy, and chemotherapy— A systematic review and meta-analysis

Cited by 6 publications

References 19 publications

The efficacy and safety of chemotherapy with or without anti‐PD‐1 for the first‐line treatment of advanced urothelial carcinoma

The efficacy and safety of chemotherapy with or without anti‐PD‐1 for the first‐line treatment of advanced urothelial carcinoma

Efficacy and Safety of Programmed Death-1/Programmed Death-Ligand 1 Inhibitor for Metastatic Urothelial Carcinoma: A Systematic Review and Meta-Analysis

New insights into ATR inhibition in muscle invasive bladder cancer: The role of apolipoprotein B mRNA editing catalytic subunit 3B

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