Clinical and molecular correlates of response to immune checkpoint blockade in urothelial carcinoma with liver metastasis

Yoshida, Takashi; Ohe, Chisato; Ito, Katsuhiro; Takada, Hiroya; Saito, Ryoichi; Kita, Yuki; Sano, Tsuyoshi; Tsuta, Koji; Kinoshita, Hidefumi; Kitamura, Hiroshi; Nishiyama, Hiroyuki; Kobayashi, Takashi

doi:10.1007/s00262-022-03204-6

Cited by 10 publications

(4 citation statements)

References 30 publications

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“…Indeed, TAMs can bind the Fc-domain glicans of anti-PD-1 antibodies on PD-1+ T cells with TAM's Fcg-receptor, thus reducing T cells exposure to anti-PD-1 antibodies (56)(57)(58)(59). TAM predictive role in neoplastic patients treated with ICI has been shown in various cancer types, as NSCLC, melanoma, glioblastoma and urothelial carcinoma (60)(61)(62)(63)(64). Further studies should be conducted to demonstrate a predictive role of TAMs also in MM.…”

Section: Tumor Immune Microenvironmentmentioning

confidence: 93%

Immunotherapy with immune checkpoint inhibitors and predictive biomarkers in malignant mesothelioma: Work still in progress

et al. 2023

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Malignant mesothelioma (MM) is a rare and aggressive neoplasm, usually associated with a poor prognosis (5 years survival rate <10%). For unresectable disease, platinum and pemetrexed chemotherapy has been the only standard of care in first line for more than two decades, while no standard treatments have been approved in subsequent lines. Recently, immunotherapy has revolutionized the therapeutic landscape of MM. In fact, the combination of ipilimumab plus nivolumab has been approved in first line setting. Moreover, immune checkpoint inhibitors (ICIs) showed promising results also in second-third line setting after platinum-based chemotherapy. Unfortunately, approximately 20% of patients are primary refractory to ICIs and there is an urgent need for reliable biomarkers to improve patient’s selection. Several biological and molecular features have been studied for this goal. In particular, histological subtype (recognized as prognostic factor for MM and predictive factor for chemotherapy response), programmed death ligand 1 (PD-L1) expression, and tumor mutational burden (widely hypothesized as predictive biomarkers for ICIs in several solid tumors) have been evaluated, but with unconclusive results. On the other hand, the deep analysis of tumor infiltrating microenvironment and the improvement in genomic profiling techniques has led to a better knowledge of several mechanisms underlying the MM biology and a greater or poorer immune activation. Consequentially, several potential biomarkers predictive of response to immunotherapy in patients with MM have been identified, also if all these elements need to be further investigated and prospectively validated.In this paper, the main evidences about clinical efficacy of ICIs in MM and the literature data about the most promising predictive biomarkers to immunotherapy are reviewed.

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Section: Tumor Immune Microenvironmentmentioning

confidence: 93%

Immunotherapy with immune checkpoint inhibitors and predictive biomarkers in malignant mesothelioma: Work still in progress

et al. 2023

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“…The major clinical risk factors were summarized in Table 2. Recently, the association between immunesuppressive tumor microenvironment and liver metastasis 48,49 or NLR 50 has been reported. Risk factors identified from real-world studies can be utilized to facilitate the understanding of ICI resistance and provide new insight to improve ICI outcomes.…”

Section: Risk Modelsmentioning

confidence: 99%

Real‐world outcomes of pembrolizumab for platinum‐refractory advanced urothelial carcinoma: Efficacy, safety, and evidence for trial‐unfit patients

2022

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Pembrolizumab, monoclonal antibody targeting programmed cell death 1, is widely used for platinum‐refractory urothelial carcinoma (UC) patients. Although the survival benefit of pembrolizumab was proven in the well‐designed phase III trial, these data represent only a part of patients due to strictly defined eligibility criteria. The patients' characteristics in the clinical practice are much more heterogenous than those of trial participants. The real‐world experience is useful to validate the trial result and find suitable candidates for the treatment. Similarly, real‐world data plays a significant role in addressing the efficacy and safety of special populations, such as poor performance status or older patients. This review summarizes the real‐world evidence on pembrolizumab for platinum‐refractory UCs and discusses the clinical risk factors and efficacy for trial‐ineligible patients.

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“…Previous studies have shown some demographic factors, such as liver metastasis, ECOG performance status and high neutrophil to lymphocyte ratio (NLR) were independent prognostic factors for patients with mUC. [12][13][14][15] Nevertheless, there are still many unknown factors that have yet to be discovered.…”

Section: Introductionmentioning

confidence: 99%

“…However, not all patients respond to ICI, and researchers are striving to identify robust biomarkers that can predict response and survival rates to ICI treatment. Previous studies have shown some demographic factors, such as liver metastasis, ECOG performance status and high neutrophil to lymphocyte ratio (NLR) were independent prognostic factors for patients with mUC 12–15 . Nevertheless, there are still many unknown factors that have yet to be discovered.…”

Section: Introductionmentioning

confidence: 99%

The impact of body mass index on survival endpoints among patients with metastatic urothelial carcinoma undergoing treatment with immune checkpoint inhibitors: A real‐world multicenter analysis

Huang,

Su,

Lin

et al. 2024

Cancer Medicine

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BackgroundStudies on the correlation between high body mass index (BMI) and extended survival among patients receiving immune checkpoint inhibitors (ICIs) have been made, although findings have shown variability. Our research explored the phenomenon of the “obesity paradox” in patients with metastatic urothelial carcinoma (mUC) undergoing treatment with ICIs.Materials and MethodsWe conducted a retrospective analysis of patients diagnosed with mUC who received a minimum of one cycle of ICI treatment at two medical centers in Taiwan from September 2015 to January 2023. Features of patients' clinicopathologic factors, including age, sex, primary or metastatic location, treatment line, and BMI were examined. The primary outcome were overall survival (OS) and progression‐free survival (PFS), which were assessed utilizing the Kaplan–Meier method. We employed the Cox‐regression model to adjust for multiple covariates.ResultsA total of 215 patients were included, with 128 (59.5%) being male, and the median age was 70 years. In the obese group (BMI ≥25 kg/m2), patients demonstrated significantly better median OS compared to the non‐obese group (BMI <25 kg/m2) (21.9 vs. 8.3 months; p = 0.021). However, there was no significant difference in median PFS between the high and low BMI groups (4.7 vs. 2.8 months; p = 0.16). Post‐hoc subgroup revealed a survival benefit from ICI treatment in male patients within the BMI ≥25 kg/m2 group (HR 0.49, 95% CI 0.30–0.81, p = 0.005).ConclusionBased on real‐world data from the Asia‐Pacific region, there appears to be a correlation between obesity and prolonged OS in patients receiving ICI treatment for mUC.

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Clinical and molecular correlates of response to immune checkpoint blockade in urothelial carcinoma with liver metastasis

Cited by 10 publications

References 30 publications

Immunotherapy with immune checkpoint inhibitors and predictive biomarkers in malignant mesothelioma: Work still in progress

Immunotherapy with immune checkpoint inhibitors and predictive biomarkers in malignant mesothelioma: Work still in progress

Real‐world outcomes of pembrolizumab for platinum‐refractory advanced urothelial carcinoma: Efficacy, safety, and evidence for trial‐unfit patients

The impact of body mass index on survival endpoints among patients with metastatic urothelial carcinoma undergoing treatment with immune checkpoint inhibitors: A real‐world multicenter analysis

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