Immune Checkpoint Inhibitors in Front-line Therapy for Urothelial Cancer

Szabados, Bernadett; Prendergast, Aaron; Jackson-Spence, Francesca; Choy, Julia; Schmid, Peter

doi:10.1016/j.euo.2021.02.010

Cited by 11 publications

(11 citation statements)

References 14 publications

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“…In recent years, the use of ICIs has made irreplaceable achievements in the treatment of BC. Atezolizumab and pembrolizumab targeting PD-1 have been approved as first-line treatment for cisplatin-ineligible metastatic urothelial BC by the Food and Drug Administration [51][52][53][54] 'Cold' tumor with low T cell infiltration is a critical reason for the resistance to immunotherapy [55,56]. It is essential to determine tumor immune cell infiltration to understand tumor progression and improve the response to immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Solute carrier family 12 member 8 (SLC12A8) is a potential biomarker and related to tumor immune cell infiltration in bladder cancer

et al. 2021

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The solute carrier family has been reported to play critical roles in the progression of several cancers; however, the relationship between solute carrier family 12 member 8 (SLC12A8) and bladder cancer (BC) has not been clearly confirmed. This study explores the prognostic value of SLC12A8 for BC and its correlation with immune cell infiltration. We found that the expression of SLC12A8 mRNA was significantly overexpressed in BC tissues compared with noncancerous tissues in multiple public databases, and the result was validated using real-time PCR and immunohistochemistry (IHC). The Kaplan-Meier method and Cox proportional hazards models were used to evaluate the prognostic value of SLC12A8 for BC. The high expression of SLC12A8 led to a shorter overall survival time and was an unfavorable prognostic biomarker for BC. The mechanisms of SLC12A8 promoting tumorigenesis were investigated by Gene Set Enrichment Analysis (GSEA). Moreover, the correlations of SLC12A8 expression with the tumor-infiltrating immune cells (TICs) in BC were explored using TIMER 2.0 and CIBERSORT. SLC12A8 was associated with CD4+ T cells, dendritic cells, neutrophils, and macrophages infiltration. The expression of SLC12A8 was positively correlated with crucial immune checkpoint molecules. In conclusion, SLC12A8 might be an unfavorable prognostic biomarker in BC related to tumor immune cell infiltration.

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Section: Discussionmentioning

confidence: 99%

Solute carrier family 12 member 8 (SLC12A8) is a potential biomarker and related to tumor immune cell infiltration in bladder cancer

et al. 2021

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“…Szabados et al. identified that immune checkpoint inhibitor monotherapy is not superior to chemotherapy as things currently stand, and the chemo-immunotherapy combination showed a probable efficacy signal, but this appeared to be insufficient to change practice ( 49 ). Huang et al.…”

Section: Discussionmentioning

confidence: 99%

The Efficacy of Intra-Arterial Plus Intravesical Chemotherapy Versus Intravesical Chemotherapy Alone After Bladder-Sparing Surgery in High-Risk Bladder Cancer: A Systematic Review and Meta-Analysis of Comparative Study

et al. 2021

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BackgroundDue to the poor prognosis, the treatment of high-risk bladder cancer (HRBC) remains controversial. This meta-analysis aims to access the efficacy of intra-arterial chemotherapy (IAC) combined with intravesical chemotherapy (IC) versus IC alone after bladder-sparing surgery in HRBC.MethodsA systematic search of PubMed, Cochrane Library databases, EMBASE (until June 2020) was conducted. PRISMA checklist was followed. The data were analyzed by RevMan v5.3.0.ResultsA total of five articles including 843 patients were studied. The analysis demonstrated that the IAC + IC group had a greater improvement of overall survival (P = 0.02) and significant reduction in terms of tumor recurrence rate (P = 0.0006) and tumor progression rate (P = 0.008) compared with the IC group. The recurrence-free survival in the IAC + IC group was significantly higher than that in the IC group (P = 0.004), but there was no significant difference in progression-free survival between the two groups (P = 0.32). In addition, the combination of IAC and IC significantly extended tumor recurrence interval (P = 0.0001) and reduced tumor-specific death rate (P = 0.01) for patients with HRBC compared with IC alone. For side effects related with IAC, although about half of the patients experienced some toxicities, most of them were mild and reversible (grades 1–2, 22.3% vs. grade 3–4, 2.7%), mainly including nausea/vomiting (P = 0.0001), neutropenia (P = 0.002), and alanine aminotransferase (P = 0.0001).ConclusionPatients with HRBC treated with IAC + IC after bladder-sparing surgery had a marked improvement in the overall survival, recurrence-free survival, time interval to first recurrence, tumor recurrence rate, tumor progression rate, and tumor-specific death rate than patients treated with IC alone. However, progression-free survival was not significantly correlated with treatment strategy. In addition, patients seemed to tolerate well the toxicities related with IAC. Systematic Review RegistrationPROSPERO, identifier CRD42021232679.

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“…The addition of avelumab as maintenance within 10 weeks of completion of first-line chemotherapy has also been shown to significantly improve OS among patients with mUC who had diseases that had not progressed with first-line chemotherapy in the phase III JAVELIN Bladder 100 trial (NCT02603432). The addition of avelumab to best supportive care is associated with an increase in median OS from 14.3 to 21.4 months with avelumab and a HR of 0.69 (95%CI: 0.56-0.86, P = 0.001) [29] .…”

Section: Maintenance Immune Therapymentioning

confidence: 96%

“…The combination ADCs together with immune therapy also shows promising new targets in phase I studies. The EV-103 study (NCT03288545) of EV in combination with pembrolizumab as first-line therapy for patients with mUC, ineligible to receive cisplatin, showed an ORR of 73.3% [29] . Results from the ongoing randomized study EV-302 (NCT04223856), comparing EV plus pembrolizumab to standard-of-care chemotherapy in the front-line setting, are awaited.…”

Section: Novel Immune Combinationsmentioning

confidence: 99%

The role of modern immunotherapy in metastatic urothelial cancer: mini review

Jackson-Spence¹,

Toms²,

Yang³

et al. 2022

J Cancer Metastasis Treat

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The approval of immune checkpoint inhibitors (ICIs) has changed the treatment landscape in many aspects of urothelial cancer (UC), in both non-muscle-invasive bladder cancer and muscle-invasive bladder cancer and has introduced the concept of long-term remission for some patients in the metastatic setting. Front-line chemotherapy remains superior at achieving initial control of disease compared to front-line immune therapy. However, long-term durable responses are limited by chemotherapy resistance. The maintenance approach, sequencing chemotherapy with ICIs, could be considered a best of both worlds approach, achieving initial control with chemotherapy, which is maintained in some individuals with avelumab. However, outcomes for patients with metastatic UC remain poor. There are three steps to improving outcomes for these patients; the first is to develop better drugs and combinations of therapies, the second is the development of novel biomarkers and techniques to better select patients for treatment, and the third area of development is to give the drugs in the most optimal setting.

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Immune Checkpoint Inhibitors in Front-line Therapy for Urothelial Cancer

Cited by 11 publications

References 14 publications

Solute carrier family 12 member 8 (SLC12A8) is a potential biomarker and related to tumor immune cell infiltration in bladder cancer

Solute carrier family 12 member 8 (SLC12A8) is a potential biomarker and related to tumor immune cell infiltration in bladder cancer

The Efficacy of Intra-Arterial Plus Intravesical Chemotherapy Versus Intravesical Chemotherapy Alone After Bladder-Sparing Surgery in High-Risk Bladder Cancer: A Systematic Review and Meta-Analysis of Comparative Study

The role of modern immunotherapy in metastatic urothelial cancer: mini review

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