Latest evidence on clinical outcomes and prognostic factors of advanced urothelial carcinoma in the era of immune checkpoint inhibitors: a narrative review

Taguchi, Satoru; Kawai, Taketo; Nakagawa, Tohru; Kume, Haruki

doi:10.1093/jjco/hyad172

Cited by 2 publications

(1 citation statement)

References 144 publications

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“…However, prospective data regarding the impact of systemic inflammation and cytokines profiles on ICIs efficacy in mUC patients are lacking (20,21). In this scenario, we have investigated the role of baseline expression of circulating cytokines and systemic inflammation indexes as prognostic biomarkers of response to avelumab maintenance in mUC patients.…”

Section: Introductionmentioning

confidence: 99%

Prognostic role of circulating cytokines and inflammation indexes for avelumab maintenance in metastatic urothelial carcinoma

Maiorano,

Schinzari,

Carbone

et al. 2024

Front. Immunol.

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BackgroundAvelumab maintenance after first-line platinum-based chemotherapy represents a cornerstone for the treatment of metastatic urothelial carcinoma (mUC). However, identifying prognostic biomarkers is paramount for optimizing patients’ benefits while minimizing toxicity. Cytokines represent circulating mediators of the complex interaction between cancer, the immune system, and inflammation. Inflammation, a hallmark of cancer, can be expressed by circulating factors. In different tumor subtypes, peripheral blood biomarkers, such as circulating cytokines, and systemic inflammatory indexes, have been addressed as potential prognostic factors for immune checkpoint inhibitors. However, their role in mUC still needs to be determined.MethodsBetween February 2021 and April 2023, we prospectively collected plasma cytokines and inflammation indexes in 28 patients with mUC before starting avelumab as first-line maintenance. The primary endpoint was the relationship between baseline cytokines and inflammatory indexes with the clinical benefit (CB), defined as the number of Responders. Secondary endpoints included the correlation of baseline cytokines and inflammatory indexes with progression-free survival (PFS), overall survival (OS), and the number and grade of immune-related adverse events.ResultsHigh pre-treatment levels of interferon (IFN)-γ and interleukin (IL)-2, and low levels of IL-6, IL-8, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and systemic-inflammation index (SII) were associated with clinical benefit and longer survival. In the multivariate analysis, low IL-8, NLR, and SII levels maintained a positive prognostic value for OS.ConclusionOur data suggest that, in mUC patients receiving avelumab, pre-treatment levels of plasma cytokines and inflammatory indexes may serve as potential prognostic biomarkers for response and efficacy. In particular, patients with signs of pre-therapeutic inflammation showed a significantly lower response and survival to avelumab. On the contrary, low systemic inflammation and high levels of cytokines characterized responders and longer survivors.

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Section: Introductionmentioning

confidence: 99%

Prognostic role of circulating cytokines and inflammation indexes for avelumab maintenance in metastatic urothelial carcinoma

Maiorano,

Schinzari,

Carbone

et al. 2024

Front. Immunol.

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Physical, but not laboratory, treatment‐related adverse events are associated with favorable outcomes of enfortumab vedotin for advanced urothelial carcinoma: A landmark analysis

Taguchi,

Kawai,

Ambe

et al. 2024

Int J of Urology

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BackgroundWhile the occurrence of immune‐related adverse events has been recognized as a prognostic marker in patients receiving immune checkpoint inhibitors, the prognostic significance of treatment‐related adverse events (trAEs) in patients undergoing antibody–drug conjugates such as enfortumab vedotin (EV) is controversial.MethodsWe reviewed 106 patients with advanced urothelial carcinoma who were treated with EV therapy at 10 institutions between 2021 and 2023. Associations of clinical parameters with overall survival and progression‐free survival were assessed using the Cox proportional hazards model. For the assessment of trAEs, landmark analysis was conducted to minimize immortal time bias.ResultsOf 106 patients, 55 (51.9%) experienced disease progression and 44 (41.5%) died during the follow‐up period. Any grade and grade ≥3 trAEs occurred in 94 (88.7%) and 44 (41.5%) patients, respectively. Common trAEs included skin disorders (74.5%), gastrointestinal disorders (62.3%), fatigue (50.0%), peripheral neuropathy (36.8%), and hematological disorders (37.7%). One patient died of interstitial pneumonia (grade 5). According to landmark analysis using 88 patients who survived for 2 months or more, trAEs were significantly associated with longer survival. Furthermore, when trAEs were classified into “physical trAEs” such as skin disorders and “laboratory trAEs” such as hematological disorders, the former were associated with longer survival while the latter were associated with shorter survival.ConclusionsPhysical, but not laboratory, trAEs are associated with favorable outcomes of EV therapy for advanced urothelial carcinoma. Both managing trAEs and utilizing them as prognostic markers are key points in the use of antibody–drug conjugates such as EV.

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Latest evidence on clinical outcomes and prognostic factors of advanced urothelial carcinoma in the era of immune checkpoint inhibitors: a narrative review

Cited by 2 publications

References 144 publications

Prognostic role of circulating cytokines and inflammation indexes for avelumab maintenance in metastatic urothelial carcinoma

Prognostic role of circulating cytokines and inflammation indexes for avelumab maintenance in metastatic urothelial carcinoma

Physical, but not laboratory, treatment‐related adverse events are associated with favorable outcomes of enfortumab vedotin for advanced urothelial carcinoma: A landmark analysis

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