Outcomes of axitinib versus sunitinib as first‐line therapy to patients with metastatic renal cell carcinoma in the immune‐oncology era

Numakura, Kazuyuki; Muto, Yumin; Naito, Sei; Hatakeyama, Shingo; Kato, Renpei; Koguchi, Tomoyuki; Kojima, Takahiro; Kawasaki, Yoshihide; Kandori, Syuya; Kawamura, Sadafumi; Arai, Yoichi; Ito, Akihiro; Nishiyama, Hiroyuki; Kojima, Yoshiyuki; Obara, Wataru; Οhyama, Chikara; Tsuchiya, Norihiko; Habuchi, Tomonori

doi:10.1002/cam4.4130

Cited by 11 publications

(11 citation statements)

References 29 publications

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“…In our clinical practice, vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) have become the standard of care for mRCC [ 31 ]. Sunitinib, a broad-spectrum inhibitor of receptor tyrosine kinases, has been widely used as the standard of treatment for first-line therapy of advanced ccRCC [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of pyroptosis regulators and tumor immune microenvironment in clear cell renal cell carcinoma

Zhang

Chen

et al. 2021

Cancer Cell Int

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Background Increasing evidence has indicated that pyroptosis could regulate the tumor immune microenvironment (TIME) to affect the tumor development. As a highly immunogenic tumor, clear cell renal cell carcinoma (ccRCC) can benefit from immunotherapy, but related research on pyroptosis in the TIME of ccRCC is still deficient. Methods Available data derived from TCGA and GEO databases were analyzed to identify the different expression profiles of pyroptosis in ccRCC and normal tissues, and the correlation of pyroptosis regulators with TIME was evaluated in ccRCC. Results According to consensus clustering analysis, two differential expression levels of subtypes were identified to affect patient prognosis, and were related to histological tumor stage and grade. Immune cells were calculated by the CIBERSORT algorithm. Higher infiltrated levels of B cells naive, T cells CD4 memory resting, NK cells resting, monocytes, macrophages were observed in Cluster 1, while higher infiltrated levels of CD8+ T cells, T follicular helper cells, and Tregs were observed in Cluster 2. Gene set enrichment analysis indicated that Cluster 2 was enriched in multiple immune-related pathways, including the JAK-STAT signaling pathway. Moreover, overexpression of eight immune checkpoints was related to ccRCC development, especially in Cluster 2. As four potentially key pyroptosis regulators, AIM2, CASP5, NOD2, and GZMB were confirmed to be upregulated in ccRCC by RT-qPCR analysis and further verified by the HPA database. Further pan-cancer analysis suggested that these four pyroptosis regulators were differentially expressed and related to the TIME in multiple cancers. Conclusion The present study provided a comprehensive view of pyroptosis regulators in the TIME of ccRCC, which may provide potential value for immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of pyroptosis regulators and tumor immune microenvironment in clear cell renal cell carcinoma

Zhang

Chen

et al. 2021

Cancer Cell Int

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“…From a therapeutic perspective, it is observed that some patients with kidney cancer develop different resistance to the most widely used drugs, such as sunitinib and axitinib, suggesting that different correlations between pyroptosis and tumor-immune microenvironments occur [ 109 , 123 , 124 ]. Moreover, different tumoral microenvironment-infiltrating cell populations are already considered an unfavorable prognostic factor for ccRCC.…”

Section: Pyroptosis In Kidney Cancermentioning

confidence: 99%

No Time to Die: How Kidney Cancer Evades Cell Death

Ganini

Montanaro

Scimeca

et al. 2022

IJMS

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The understanding of the pathogenesis of renal cell carcinoma led to the development of targeted therapies, which dramatically changed the overall survival rate. Nonetheless, despite innovative lines of therapy accessible to patients, the prognosis remains severe in most cases. Kidney cancer rarely shows mutations in the genes coding for proteins involved in programmed cell death, including p53. In this paper, we show that the molecular machinery responsible for different forms of cell death, such as apoptosis, ferroptosis, pyroptosis, and necroptosis, which are somehow impaired in kidney cancer to allow cancer cell growth and development, was reactivated by targeted pharmacological intervention. The aim of the present review was to summarize the modality of programmed cell death in the pathogenesis of renal cell carcinoma, showing in vitro and in vivo evidence of their potential role in controlling kidney cancer growth, and highlighting their possible therapeutic value.

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“… 7 , 8 , 9 , 10 , 11 , 12 Treatment with ICIs in combination or ICIs plus TKIs is considered the standard of care for patients with metastatic RCC. 13 , 14 , 15 , 16 , 17 , 18 Furthermore, immune‐related AEs are closely associated with high‐dose steroid administration in patients treated with ICIs, and steroid use has been associated with impaired humoral response to SARS‐CoV‐2 mRNA vaccines in patients with cancer. 5 , 19 , 20 However, the effect of different types of anticancer therapy and the concomitant use of steroids on antibody responses to SARS‐CoV‐2 vaccines in patients with UC and RCC remains unknown.…”

Section: Introductionmentioning

confidence: 99%

“…Systemic chemotherapy and ICIs are two immunoregulation agents frequently administered to patients with advanced UC 7–12 . Treatment with ICIs in combination or ICIs plus TKIs is considered the standard of care for patients with metastatic RCC 13–18 . Furthermore, immune‐related AEs are closely associated with high‐dose steroid administration in patients treated with ICIs, and steroid use has been associated with impaired humoral response to SARS‐CoV‐2 mRNA vaccines in patients with cancer 5,19,20 .…”

Section: Introductionmentioning

confidence: 99%

Effect of active anticancer therapy on serologic response to SARS‐CoV‐2 BNT162b2 vaccine in patients with urothelial and renal cell carcinoma

et al. 2022

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Objectives To evaluate the serologic response to the BNT162b2 messenger ribonucleic acid vaccine in patients with urothelial carcinoma and renal cell carcinoma. Methods Between June 2021 and November 2021, we retrospectively evaluated blood samples from 60 healthy controls (control group), 57 patients with urothelial carcinoma, and 28 patients with renal cell carcinoma who had received two doses of the BNT162b2 vaccine at Hirosaki University Hospital. We determined the immunoglobulin G antibody titers against the severe acute respiratory syndrome coronavirus 2 spike receptor‐binding domain. Seropositivity was defined as ≥15 U/mL. We investigate factors associated with antibody titers and seropositivity in the patients with urothelial carcinoma and renal cell carcinoma. Results Antibody titers in the control, urothelial carcinoma, and renal cell carcinoma groups were 813, 431, and 500 U/mL, respectively. Seropositivity was 100%, 90%, and 96% in the control, urothelial carcinoma, and renal cell carcinoma groups, respectively. Of the 85 patients, 37 of 57 (65%) and 21 of 28 (75%) were actively undergoing anticancer treatment for urothelial carcinoma and renal cell carcinoma, respectively. Anti‐severe acute respiratory syndrome coronavirus 2 spike immunoglobulin G antibody titers and seropositivity was not significantly different between the patients with urothelial carcinoma and renal cell carcinoma. Anti‐severe acute respiratory syndrome coronavirus 2 spike immunoglobulin G antibody titers were not significantly associated with active anticancer therapy or steroid treatment for immune‐related adverse events. Univariable logistic regression analysis revealed that older age and metastatic disease were significantly and negatively associated with seropositivity. Conclusions Patients with urothelial carcinoma or renal cell carcinoma exhibited an adequate antibody response to the BNT162b2 vaccine. Active anticancer therapy was not significantly associated with seropositivity following vaccination with severe acute respiratory syndrome coronavirus 2 BNT162b2 in patients with urothelial carcinoma and renal cell carcinoma.

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Outcomes of axitinib versus sunitinib as first‐line therapy to patients with metastatic renal cell carcinoma in the immune‐oncology era

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 11 publications

References 29 publications

Comprehensive analysis of pyroptosis regulators and tumor immune microenvironment in clear cell renal cell carcinoma

Comprehensive analysis of pyroptosis regulators and tumor immune microenvironment in clear cell renal cell carcinoma

No Time to Die: How Kidney Cancer Evades Cell Death

Effect of active anticancer therapy on serologic response to SARS‐CoV‐2 BNT162b2 vaccine in patients with urothelial and renal cell carcinoma

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