Harrison C. Gottlich, Reza Nabavizadeh, Mihai Dumbrava, Rodrigo Rodrigues Pessoa, Ahmed M. Mahmoud, Ishita Garg, Jacob J. Orme, B. A. Costello, John Cheville, Fabrice Lucien
Background: Approximately 30% of renal cell carcinoma (RCC) cases present with de novo metastatic disease, while 20% to 30% of those with localized disease will develop metastases following surgical resection. Various drug classes have been investigated to treat RCC, including cytokine-based therapies, small molecule Vascular Endothelial Growth Factor (VEGF) tyrosine kinase inhibitors (TKIs) and antibody-based therapies. Up to 58% of patients fail to respond to primary immune checkpoint inhibitor (ICI) therapy, and nearly all initial responders experience disease progression due to the development of secondary resistance. Consequently, novel treatment options are being investigated. Objective: Review the rapidly evolving ADC therapeutic landscape in metastatic RCC including recent trials, emerging ADCs targets, and future directions for ADCs in the treatment of advanced RCC. Methods: Literature review using the MEDLINE database on important trials and presentations from the American Society of Clinical Oncology (ASCO), and the European Society for Medical Oncology (ESMO) conferences. Key words used included “renal cell carcinoma,” “RCC,” “metastatic RCC,” “advanced RCC,” “antibody-based therapies,” “immunotherapy,” “clinical trials,” and “emerging drugs.” Specifically for review of ADCs in RCC, the following search string was used with additional review of bibliographies from retrieved papers: “((antibody drug conjugate) OR (antibody-dependent cellular cytotoxicity) OR (chimeric antigen receptor)) AND ((kidney cancer) OR (renal cell carcinoma))”. Results: Several promising targets including MMP14, EGFR, MCT4, CA9, MET, CDH13, B7-H3, and PSMA were identified with relevant preclinical and clinical studies reviewed. Conclusions: While ADCs therapeutics have not shown benefit to date for renal cell carcinoma, there are ample promising candidates and targets for future research.
{"title":"Emerging Antibody-Drug Conjugate Therapies and Targets for Metastatic Renal Cell Carcinoma","authors":"Harrison C. Gottlich, Reza Nabavizadeh, Mihai Dumbrava, Rodrigo Rodrigues Pessoa, Ahmed M. Mahmoud, Ishita Garg, Jacob J. Orme, B. A. Costello, John Cheville, Fabrice Lucien","doi":"10.3233/kca-230012","DOIUrl":"https://doi.org/10.3233/kca-230012","url":null,"abstract":"Background: Approximately 30% of renal cell carcinoma (RCC) cases present with de novo metastatic disease, while 20% to 30% of those with localized disease will develop metastases following surgical resection. Various drug classes have been investigated to treat RCC, including cytokine-based therapies, small molecule Vascular Endothelial Growth Factor (VEGF) tyrosine kinase inhibitors (TKIs) and antibody-based therapies. Up to 58% of patients fail to respond to primary immune checkpoint inhibitor (ICI) therapy, and nearly all initial responders experience disease progression due to the development of secondary resistance. Consequently, novel treatment options are being investigated. Objective: Review the rapidly evolving ADC therapeutic landscape in metastatic RCC including recent trials, emerging ADCs targets, and future directions for ADCs in the treatment of advanced RCC. Methods: Literature review using the MEDLINE database on important trials and presentations from the American Society of Clinical Oncology (ASCO), and the European Society for Medical Oncology (ESMO) conferences. Key words used included “renal cell carcinoma,” “RCC,” “metastatic RCC,” “advanced RCC,” “antibody-based therapies,” “immunotherapy,” “clinical trials,” and “emerging drugs.” Specifically for review of ADCs in RCC, the following search string was used with additional review of bibliographies from retrieved papers: “((antibody drug conjugate) OR (antibody-dependent cellular cytotoxicity) OR (chimeric antigen receptor)) AND ((kidney cancer) OR (renal cell carcinoma))”. Results: Several promising targets including MMP14, EGFR, MCT4, CA9, MET, CDH13, B7-H3, and PSMA were identified with relevant preclinical and clinical studies reviewed. Conclusions: While ADCs therapeutics have not shown benefit to date for renal cell carcinoma, there are ample promising candidates and targets for future research.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" 6","pages":""},"PeriodicalIF":1.2,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139144541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Akasha Dukkipati, Xiaochen Li, S. Pal, Miguel Zugman
Background: The nephrotoxicity profile of contemporary first-line regimens for treatment of metastatic renal cell carcinoma (mRCC) has not been systematically studied in published clinical trials. Objective: To assess the rates of nephrotoxic events of contemporary first-line regimens for treatment of mRCC in comparison to vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI) mono-therapy. Methods: We performed a systematic search of the literature looking for randomized clinical trials that contemplated National Comprehensive Cancer Network (NCCN) recommended first-line regimens for treating mRCC in which the control arm was a VEGF-TKI. Selected trials could either include an experimental arm of immune checkpoint inhibitor (ICI) plus VEGF-TKI combination or ICI-ICI combination. Nephrotoxic events were defined as proteinuria, hypertension, blood creatinine increase, acute kidney failure or nephritis, which were all described separately. Results: Five studies satisfied our inclusion criteria. Combination of ICI with VEGF-TKI showed a statistically significant higher degree of proteinuria compared to VEGF-TKI alone. There was no statistically significant difference in rates of hypertension between ICI-TKI and VEGF-TKI alone, but VEGF-TKI alone was statistically significantly more associated with hypertension than immunotherapy alone. Other renal toxicities, such as an increase in creatinine, acute kidney injury (AKI) and nephritis, were uncommon and not consistently reported in each trial. Conclusions: Contemporary regimens for first-line treatment of mRCC are associated with a higher grade of proteinuria than VEGF-TKI alone, while VEGF-TKI is more associated with hypertension than an ICI-ICI combination. Description of many renal toxicities across the studies reported have been diverse and a standardized definition across clinical trials would be helpful to reliably interpret the data regarding nephrotoxicity in the setting of treatment of renal cell carcinoma.
{"title":"Nephrotoxicity Associated with Contemporary Renal Cell Carcinoma Regimens: A Systematic Review and Meta-Analysis","authors":"Akasha Dukkipati, Xiaochen Li, S. Pal, Miguel Zugman","doi":"10.3233/kca-230018","DOIUrl":"https://doi.org/10.3233/kca-230018","url":null,"abstract":"Background: The nephrotoxicity profile of contemporary first-line regimens for treatment of metastatic renal cell carcinoma (mRCC) has not been systematically studied in published clinical trials. Objective: To assess the rates of nephrotoxic events of contemporary first-line regimens for treatment of mRCC in comparison to vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI) mono-therapy. Methods: We performed a systematic search of the literature looking for randomized clinical trials that contemplated National Comprehensive Cancer Network (NCCN) recommended first-line regimens for treating mRCC in which the control arm was a VEGF-TKI. Selected trials could either include an experimental arm of immune checkpoint inhibitor (ICI) plus VEGF-TKI combination or ICI-ICI combination. Nephrotoxic events were defined as proteinuria, hypertension, blood creatinine increase, acute kidney failure or nephritis, which were all described separately. Results: Five studies satisfied our inclusion criteria. Combination of ICI with VEGF-TKI showed a statistically significant higher degree of proteinuria compared to VEGF-TKI alone. There was no statistically significant difference in rates of hypertension between ICI-TKI and VEGF-TKI alone, but VEGF-TKI alone was statistically significantly more associated with hypertension than immunotherapy alone. Other renal toxicities, such as an increase in creatinine, acute kidney injury (AKI) and nephritis, were uncommon and not consistently reported in each trial. Conclusions: Contemporary regimens for first-line treatment of mRCC are associated with a higher grade of proteinuria than VEGF-TKI alone, while VEGF-TKI is more associated with hypertension than an ICI-ICI combination. Description of many renal toxicities across the studies reported have been diverse and a standardized definition across clinical trials would be helpful to reliably interpret the data regarding nephrotoxicity in the setting of treatment of renal cell carcinoma.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"21 4","pages":""},"PeriodicalIF":1.2,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139173084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Tripathi, L. Meza, N. Sayegh, Ameish Govindarajan, Sara A. Byron, Jiaming Zhang, B. Chigarira, Y. Jo, Z. Zengin, Haoran Li, G. Gebrael, A. Desai, N. Agarwal, U. Swami, B. Maughan, S. Pal
Background: Ipilimumab plus nivolumab is approved as a first-line treatment for intermediate or poor risk metastatic renal cell carcinoma (mRCC). However, ∼35% of patients progress within six months on ipilimumab plus nivolumab, and no validated genomic biomarkers predict the benefit. In this study, we explore the genomic and transcriptomic differences among patients with clear cell mRCC patients who either did or did not experience clinical benefit from first-line ipilimumab plus nivolumab therapy. Method: Patients with clear cell mRCC intermediate or poor IMDC risk scores, with available tumor whole exome with/without transcriptome sequencing before starting systemic therapy were included. Patients who developed a complete response, partial response, or stable disease for at least six months after initiating treatment were categorized into the ‘clinical benefit’ group, whereas the rest were classified as ‘no clinical benefit.’ Genomic alteration frequencies between the groups were assessed with a chi-square test. Differentially expressed genes and gene sets were identified via DeSeq2 and GSEA v4.2.3, respectively. Result: 53 patients with clear cell mRCC (37 clinical benefit and 16 no clinical benefit) were eligible and included. No significant difference was found in the genomic alteration frequencies between these groups. Baseline tumor transcriptomic data were available for 14 patients (9 clinical benefit and 5 no clinical benefit). The apical surface and pathways downregulated by KRAS signaling were enriched in the clinical benefit group, whereas inflammatory pathways were enriched in the no clinical benefit group. Conclusion: These findings suggest that tumor specific gene expression as assessed by RNA sequencing could serve as a potential biomarker of response to ipilimumab plus nivolumab therapy.
{"title":"Genomic and Transcriptomic Characteristics of Tumors of Patients with Metastatic Clear Cell Renal Cell Carcinoma Clinically Benefiting from First-Line Treatment with Ipilimumab Plus Nivolumab","authors":"N. Tripathi, L. Meza, N. Sayegh, Ameish Govindarajan, Sara A. Byron, Jiaming Zhang, B. Chigarira, Y. Jo, Z. Zengin, Haoran Li, G. Gebrael, A. Desai, N. Agarwal, U. Swami, B. Maughan, S. Pal","doi":"10.3233/kca-230011","DOIUrl":"https://doi.org/10.3233/kca-230011","url":null,"abstract":"Background: Ipilimumab plus nivolumab is approved as a first-line treatment for intermediate or poor risk metastatic renal cell carcinoma (mRCC). However, ∼35% of patients progress within six months on ipilimumab plus nivolumab, and no validated genomic biomarkers predict the benefit. In this study, we explore the genomic and transcriptomic differences among patients with clear cell mRCC patients who either did or did not experience clinical benefit from first-line ipilimumab plus nivolumab therapy. Method: Patients with clear cell mRCC intermediate or poor IMDC risk scores, with available tumor whole exome with/without transcriptome sequencing before starting systemic therapy were included. Patients who developed a complete response, partial response, or stable disease for at least six months after initiating treatment were categorized into the ‘clinical benefit’ group, whereas the rest were classified as ‘no clinical benefit.’ Genomic alteration frequencies between the groups were assessed with a chi-square test. Differentially expressed genes and gene sets were identified via DeSeq2 and GSEA v4.2.3, respectively. Result: 53 patients with clear cell mRCC (37 clinical benefit and 16 no clinical benefit) were eligible and included. No significant difference was found in the genomic alteration frequencies between these groups. Baseline tumor transcriptomic data were available for 14 patients (9 clinical benefit and 5 no clinical benefit). The apical surface and pathways downregulated by KRAS signaling were enriched in the clinical benefit group, whereas inflammatory pathways were enriched in the no clinical benefit group. Conclusion: These findings suggest that tumor specific gene expression as assessed by RNA sequencing could serve as a potential biomarker of response to ipilimumab plus nivolumab therapy.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"29 37","pages":""},"PeriodicalIF":1.2,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138995614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Non-clear cell renal cell carcinoma (nccRCC) is a diverse group of cancers that occurs in approximately 25% of patients with renal cell carcinoma. In the advanced/metastatic setting, survival in all nccRCC subtypes is considered poor, due to the inherent aggressiveness of these cancers, and a lack of effective systemic treatment options. Clinical trials of immune/targeted agents have predominantly focused on patients with ccRCC. There is no globally accepted standard of care for nccRCC; however, recently clinical trials have been initiated in this population. Objective: To perform a targeted literature review of published original observational studies reporting common real-world clinical outcomes (real-world overall response rate [rwORR], real-world progression free survival [rwPFS], real-world overall survival [rwOS]) in previously treatment naïve patients with advanced/metastatic nccRCC. Methods: A targeted search of MEDLINE and EMBASE was conducted per PRISMA guidelines to identify observational studies in previously treatment naïve patients with advanced/metastatic nccRCC. Publications with adequate information since 2010 and from select conferences since 2020 were considered. Results: 27 studies across 29 publications were identified. Sample sizes ranged from 7-1,573 across these studies with differences in nccRCC subtypes included and treatments received. Real-world ORR ranged from 0–37%, median rwPFS from 2–17 months, and median rwOS from 3–30 months, across 19, 17, and 24 studies, respectively. These outcomes also varied with receipt/type of treatment and demographic/clinical subgroups with outcomes tending to be worse in patients with papillary RCC compared to chromophobe RCC. Conclusions: Clinical outcomes varied, as patient populations, eligible histologies, treatments and methods were heterogeneous.
{"title":"Targeted Literature Review of Outcomes to Initial Systemic Therapy for Advanced/Metastatic Non-Clear Cell Renal Cell Carcinoma in Observational Studies","authors":"Shawna R. Calhoun, Manish Sharma, Chung-Han Lee","doi":"10.3233/kca-230008","DOIUrl":"https://doi.org/10.3233/kca-230008","url":null,"abstract":"Background: Non-clear cell renal cell carcinoma (nccRCC) is a diverse group of cancers that occurs in approximately 25% of patients with renal cell carcinoma. In the advanced/metastatic setting, survival in all nccRCC subtypes is considered poor, due to the inherent aggressiveness of these cancers, and a lack of effective systemic treatment options. Clinical trials of immune/targeted agents have predominantly focused on patients with ccRCC. There is no globally accepted standard of care for nccRCC; however, recently clinical trials have been initiated in this population. Objective: To perform a targeted literature review of published original observational studies reporting common real-world clinical outcomes (real-world overall response rate [rwORR], real-world progression free survival [rwPFS], real-world overall survival [rwOS]) in previously treatment naïve patients with advanced/metastatic nccRCC. Methods: A targeted search of MEDLINE and EMBASE was conducted per PRISMA guidelines to identify observational studies in previously treatment naïve patients with advanced/metastatic nccRCC. Publications with adequate information since 2010 and from select conferences since 2020 were considered. Results: 27 studies across 29 publications were identified. Sample sizes ranged from 7-1,573 across these studies with differences in nccRCC subtypes included and treatments received. Real-world ORR ranged from 0–37%, median rwPFS from 2–17 months, and median rwOS from 3–30 months, across 19, 17, and 24 studies, respectively. These outcomes also varied with receipt/type of treatment and demographic/clinical subgroups with outcomes tending to be worse in patients with papillary RCC compared to chromophobe RCC. Conclusions: Clinical outcomes varied, as patient populations, eligible histologies, treatments and methods were heterogeneous.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"92 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136255237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ilya Tsimafeyeu, Gunel Musaeva, Igor Utyashev, Kristina Zakurdaeva, Ivan Gerk, Olshanskaya Anna, Samira Mahmudova, Nana Otkhozoria, Maria Volkova, Timur Mitin
Background: Introduction of immune checkpoint inhibitors in the standard of care for metastatic renal cell carcinoma (mRCC) requires robust but yet simple biomarkers to predict efficacy of immunotherapy. Objective: The aim of this study was to evaluate the association between fibrinogen levels and efficacy of second-line therapy with nivolumab in mRCC. Methods: This is a prospective multicenter biomarker study. Fibrinogen levels were measured one week prior to second-line nivolumab therapy and six times monthly. A high fibrinogen level was defined as ≥5 g/L. Patients were divided into two cohorts: high (H) and normal (N) fibrinogen levels. The primary endpoint was overall survival (OS). Results: The median OS was 31.5 months (95% confidence interval [CI], 27.9 to 35.1) in cohort N vs. 20.9 months (95% CI, 18.1 to 23.7) in cohort H (hazard ratio [HR], 0.39; 98.5% CI, 0.21 to 0.7; P = 0.002). The median progression-free survival was 9.4 months (95% CI, 5.5 to 14.1) in cohort N and 4.0 months (95% CI, 2.9 to 5.1) in cohort H (HR, 0.65; 95% CI, 0.51 to 0.72; P < 0.001). The objective response rate was higher in N cohort (33% vs. 17% ; P = 0.012). No statistically significant changes of fibrinogen concentration during nivolumab therapy were found. Conclusion: The study demonstrated an association of hyperfibrinogenemia with worse clinical outcomes of second-line nivolumab monotherapy in patients with mRCC. Further validation of fibrinogen as a predictive biomarker for immunotherapy efficacy in patients with mRCC is warranted.
{"title":"Fibrinogen Levels in Patients with Metastatic Renal Cell Carcinoma Treated with Nivolumab: Results of a Multicenter Prospective Trial","authors":"Ilya Tsimafeyeu, Gunel Musaeva, Igor Utyashev, Kristina Zakurdaeva, Ivan Gerk, Olshanskaya Anna, Samira Mahmudova, Nana Otkhozoria, Maria Volkova, Timur Mitin","doi":"10.3233/kca-230007","DOIUrl":"https://doi.org/10.3233/kca-230007","url":null,"abstract":"Background: Introduction of immune checkpoint inhibitors in the standard of care for metastatic renal cell carcinoma (mRCC) requires robust but yet simple biomarkers to predict efficacy of immunotherapy. Objective: The aim of this study was to evaluate the association between fibrinogen levels and efficacy of second-line therapy with nivolumab in mRCC. Methods: This is a prospective multicenter biomarker study. Fibrinogen levels were measured one week prior to second-line nivolumab therapy and six times monthly. A high fibrinogen level was defined as ≥5 g/L. Patients were divided into two cohorts: high (H) and normal (N) fibrinogen levels. The primary endpoint was overall survival (OS). Results: The median OS was 31.5 months (95% confidence interval [CI], 27.9 to 35.1) in cohort N vs. 20.9 months (95% CI, 18.1 to 23.7) in cohort H (hazard ratio [HR], 0.39; 98.5% CI, 0.21 to 0.7; P = 0.002). The median progression-free survival was 9.4 months (95% CI, 5.5 to 14.1) in cohort N and 4.0 months (95% CI, 2.9 to 5.1) in cohort H (HR, 0.65; 95% CI, 0.51 to 0.72; P < 0.001). The objective response rate was higher in N cohort (33% vs. 17% ; P = 0.012). No statistically significant changes of fibrinogen concentration during nivolumab therapy were found. Conclusion: The study demonstrated an association of hyperfibrinogenemia with worse clinical outcomes of second-line nivolumab monotherapy in patients with mRCC. Further validation of fibrinogen as a predictive biomarker for immunotherapy efficacy in patients with mRCC is warranted.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"71 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135302194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Ibañez Vázquez, Pablo Abad López, Juan Gómez Rivas, I. De La Parra Sánchez, Dimitry Enikeev, Álvaro Serrano Pascual, Lorena Fernández Montarroso, Esther García Rojo, Jesús Moreno Sierra
BACKGROUND: Renal cysts are the most frequently occurring incidental renal lesions. They are asymptomatic, which explains why they tend to be diagnosed incidentally as a result of imaging tests. In cases where malignancy is suspected, there are various therapeutic alternatives. OBJECTIVE: The objective of this study is to review the diagnostic and therapeutic alternatives for cystic renal lesions. METHOD: A systematic search was conducted in Pubmed, Science Direct, Scopus, and Google Scholar databases between May and October 2022. The review of articles was conducted following the methodological recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 Statement. As a result, 25 articles were selected. RESULTS: Thirteen studies focused on diagnostic management. In five of the cases ultrasound was used, multiparametric magnetic resonance imaging (mpMRI) was considered in six articles, and computerized tomography (CT) was studied in three. Eleven papers were retrospective series, one of the studies was prospective, and one was a simulated cost-effectiveness model. Among the 12 articles on treatment, five focused on surgery and one on the results of active surveillance, while three compared active surveillance with other treatments. Four articles assessed the percutaneous approach and radiofrequency ablation. All articles were retrospective cohorts. CONCLUSIONS: CT is the most standard of the tests. In doubtful cases, mpMRI and ultrasound can serve as complementary tests. Partial nephrectomy is currently the gold standard treatment and the results are similar for both open and laparoscopic approaches. Percutaneous radiofrequency treatments produce reasonable survival rates free of local recurrence and metastasis and are recommended in patients with high surgical risk.
{"title":"Cystic Renal Lesions: A Systematic Review of Diagnosis and Treatment","authors":"L. Ibañez Vázquez, Pablo Abad López, Juan Gómez Rivas, I. De La Parra Sánchez, Dimitry Enikeev, Álvaro Serrano Pascual, Lorena Fernández Montarroso, Esther García Rojo, Jesús Moreno Sierra","doi":"10.3233/kca-230002","DOIUrl":"https://doi.org/10.3233/kca-230002","url":null,"abstract":"BACKGROUND: Renal cysts are the most frequently occurring incidental renal lesions. They are asymptomatic, which explains why they tend to be diagnosed incidentally as a result of imaging tests. In cases where malignancy is suspected, there are various therapeutic alternatives. OBJECTIVE: The objective of this study is to review the diagnostic and therapeutic alternatives for cystic renal lesions. METHOD: A systematic search was conducted in Pubmed, Science Direct, Scopus, and Google Scholar databases between May and October 2022. The review of articles was conducted following the methodological recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 Statement. As a result, 25 articles were selected. RESULTS: Thirteen studies focused on diagnostic management. In five of the cases ultrasound was used, multiparametric magnetic resonance imaging (mpMRI) was considered in six articles, and computerized tomography (CT) was studied in three. Eleven papers were retrospective series, one of the studies was prospective, and one was a simulated cost-effectiveness model. Among the 12 articles on treatment, five focused on surgery and one on the results of active surveillance, while three compared active surveillance with other treatments. Four articles assessed the percutaneous approach and radiofrequency ablation. All articles were retrospective cohorts. CONCLUSIONS: CT is the most standard of the tests. In doubtful cases, mpMRI and ultrasound can serve as complementary tests. Partial nephrectomy is currently the gold standard treatment and the results are similar for both open and laparoscopic approaches. Percutaneous radiofrequency treatments produce reasonable survival rates free of local recurrence and metastasis and are recommended in patients with high surgical risk.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46890647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-11eCollection Date: 2023-01-01DOI: 10.3233/KCA-230006
Nicholas R Schindler, David A Braun
Immune checkpoint inhibitors (ICIs) have transformed the management of advanced renal cell carcinoma (RCC), but most patients still do not receive a long-term benefit from these therapies, and many experience off-target, immune-related adverse effects. RCC is also different from many other ICI-responsive tumors, as it has only a modest mutation burden, and total neoantigen load does not correlate with ICI response. In order to improve the efficacy and safety of immunotherapies for RCC, it is therefore critical to identify the antigens that are targeted in effective anti-tumor immunity. In this review, we describe the potential classes of target antigens, and provide examples of previous and ongoing efforts to investigate and target antigens in RCC, with a focus on clear cell histology. Ultimately, we believe that a concerted antigen discovery effort in RCC will enable an improved understanding of response and resistance to current therapies, and lay a foundation for the future development of "precision" antigen-directed immunotherapies.
{"title":"Antigenic targets in clear cell renal cell carcinoma.","authors":"Nicholas R Schindler, David A Braun","doi":"10.3233/KCA-230006","DOIUrl":"10.3233/KCA-230006","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have transformed the management of advanced renal cell carcinoma (RCC), but most patients still do not receive a long-term benefit from these therapies, and many experience off-target, immune-related adverse effects. RCC is also different from many other ICI-responsive tumors, as it has only a modest mutation burden, and total neoantigen load does not correlate with ICI response. In order to improve the efficacy and safety of immunotherapies for RCC, it is therefore critical to identify the antigens that are targeted in effective anti-tumor immunity. In this review, we describe the potential classes of target antigens, and provide examples of previous and ongoing efforts to investigate and target antigens in RCC, with a focus on clear cell histology. Ultimately, we believe that a concerted antigen discovery effort in RCC will enable an improved understanding of response and resistance to current therapies, and lay a foundation for the future development of \"precision\" antigen-directed immunotherapies.</p>","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"7 1","pages":"81-91"},"PeriodicalIF":1.2,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10475986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70126903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUND: Papillary renal cell carcinoma (PRCC) has a relatively poor prognosis in the metastatic setting. In contrast to clear cell kidney cancer, there are limited treatment options specifically tested in PRCC. Alterations in the MET pathway are common in PRCC and may play a pivotal role in promoting tumor growth and the development of resistance to systemic therapy. OBJECTIVE: Current data on the efficacy of MET inhibitors over standard of care in PRCC is immature and evolving. The purpose of this systematic review is to assess and summarize the results and limitations of landmark trials of MET inhibitors for PRCC as well as to discuss barriers faced by trials of these drugs. METHODS: Manuscripts and abstracts were collected from PubMed, the American Society of Clinical Oncology (ASCO) historical abstracts and European Society for Medical Oncology (ESMO) historical abstracts. Included studies must have been either a clinical trial, systematic review or narrative review and included PRCC patients. Patients must have been treated with a selective or non-selective MET inhibitor. After the final application of criteria, 30 studies were included. RESULTS/CONCLUSIONS: Cabozantinib has the best evidence for use showing improved outcomes in PRCC. Other MET inhibitors, including savolitinib, crizotinib, and foretinib have shown possible benefit in patients with MET-positive disease, but the inconsistent definition of MET status and a low patient accrual rate prevented further extrapolation of the individual trial results. Future trials of single agent savolitinib, as well as combination MET inhibitor/ immuno-oncology (IO) therapies, have the potential to change the therapeutic landscape of using MET inhibitors for PRCC.
{"title":"MET Inhibitors for Papillary Renal Cell Carcinoma","authors":"J. Brundage, Kamalakanta Sahu, B. Maughan","doi":"10.3233/kca-230005","DOIUrl":"https://doi.org/10.3233/kca-230005","url":null,"abstract":"BACKGROUND: Papillary renal cell carcinoma (PRCC) has a relatively poor prognosis in the metastatic setting. In contrast to clear cell kidney cancer, there are limited treatment options specifically tested in PRCC. Alterations in the MET pathway are common in PRCC and may play a pivotal role in promoting tumor growth and the development of resistance to systemic therapy. OBJECTIVE: Current data on the efficacy of MET inhibitors over standard of care in PRCC is immature and evolving. The purpose of this systematic review is to assess and summarize the results and limitations of landmark trials of MET inhibitors for PRCC as well as to discuss barriers faced by trials of these drugs. METHODS: Manuscripts and abstracts were collected from PubMed, the American Society of Clinical Oncology (ASCO) historical abstracts and European Society for Medical Oncology (ESMO) historical abstracts. Included studies must have been either a clinical trial, systematic review or narrative review and included PRCC patients. Patients must have been treated with a selective or non-selective MET inhibitor. After the final application of criteria, 30 studies were included. RESULTS/CONCLUSIONS: Cabozantinib has the best evidence for use showing improved outcomes in PRCC. Other MET inhibitors, including savolitinib, crizotinib, and foretinib have shown possible benefit in patients with MET-positive disease, but the inconsistent definition of MET status and a low patient accrual rate prevented further extrapolation of the individual trial results. Future trials of single agent savolitinib, as well as combination MET inhibitor/ immuno-oncology (IO) therapies, have the potential to change the therapeutic landscape of using MET inhibitors for PRCC.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2023-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42799114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical Trials Corner: The Challenge to Establish Optimal Treatment After Progression on Checkpoint Inhibitors","authors":"M. Parikh","doi":"10.3233/kca-239002","DOIUrl":"https://doi.org/10.3233/kca-239002","url":null,"abstract":"","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48460183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Uhlig, Johannes Uhlig, M. Woike, Thomas Fischer, L. Trojan, L. Bergmann, M. Bögemann, P. Goebell, M. Rink, K. Schlack, M. Leitsmann, A. Strauß
Objective: To evaluate the effectiveness and safety profile of the tyrosine kinase inhibitor Axitinib for patients with advanced or metastatic renal cell carcinoma (a/mRCC) in a real-world setting. Methods: Adult patients from the German non-interventional post-approval multicenter STAR-TOR registry with a/mRCC (NCT00700258) were included if treated with Axitinib in second line or beyond. Overall survival (OS), progression-free survival (PFS) and adverse events were evaluated across subgroups using descriptive statistics and survival analyses. Results: Between November 2012 and December 2020, 75 study sites recruited 210 patients treated with Axitinib (69,6% male; median age 69 years; median Karnofsky Index 80%). Clear cell RCC was the most frequent histological subtype (81.0%). Axitinib was administered as second-line in 51.4%, third-line in 24.8%, and fourth-line treatment and beyond in 23.8% of the patients, respectively. MSKCC score was 15.0% favorable, 33.6% intermediate, and 51.3% poor risk. Median PFS was 5.6 months, and median OS 18.3 months. Patients with lactate dehydrogenase (LDH) levels > 300U/l had a nominally significantly shorter OS than patients with LDH≤300U/l (8.2 vs. 19.0 months, p = 0.008). Drug related adverse and serious adverse events were reported in 56.7% and 17.6% of the patients, respectively (most common adverse event: gastrointestinal disorders; 37.6%). Conclusions: This real-world study confirms the clinical relevance of Axitinib in the second-line and beyond setting for a/mRCC with OS and PFS reported in concordance with pivotal trials, while demonstrating a favorable safety profile. A high LDH serum level could be a negative predictive marker for Axitinib effectiveness, which can aid in clinical decision making.
{"title":"Axitinib beyond first-line therapy of Metastatic Renal Cell Carcinoma: Real World Data from the STAR-TOR registry","authors":"A. Uhlig, Johannes Uhlig, M. Woike, Thomas Fischer, L. Trojan, L. Bergmann, M. Bögemann, P. Goebell, M. Rink, K. Schlack, M. Leitsmann, A. Strauß","doi":"10.3233/kca-220011","DOIUrl":"https://doi.org/10.3233/kca-220011","url":null,"abstract":"Objective: To evaluate the effectiveness and safety profile of the tyrosine kinase inhibitor Axitinib for patients with advanced or metastatic renal cell carcinoma (a/mRCC) in a real-world setting. Methods: Adult patients from the German non-interventional post-approval multicenter STAR-TOR registry with a/mRCC (NCT00700258) were included if treated with Axitinib in second line or beyond. Overall survival (OS), progression-free survival (PFS) and adverse events were evaluated across subgroups using descriptive statistics and survival analyses. Results: Between November 2012 and December 2020, 75 study sites recruited 210 patients treated with Axitinib (69,6% male; median age 69 years; median Karnofsky Index 80%). Clear cell RCC was the most frequent histological subtype (81.0%). Axitinib was administered as second-line in 51.4%, third-line in 24.8%, and fourth-line treatment and beyond in 23.8% of the patients, respectively. MSKCC score was 15.0% favorable, 33.6% intermediate, and 51.3% poor risk. Median PFS was 5.6 months, and median OS 18.3 months. Patients with lactate dehydrogenase (LDH) levels > 300U/l had a nominally significantly shorter OS than patients with LDH≤300U/l (8.2 vs. 19.0 months, p = 0.008). Drug related adverse and serious adverse events were reported in 56.7% and 17.6% of the patients, respectively (most common adverse event: gastrointestinal disorders; 37.6%). Conclusions: This real-world study confirms the clinical relevance of Axitinib in the second-line and beyond setting for a/mRCC with OS and PFS reported in concordance with pivotal trials, while demonstrating a favorable safety profile. A high LDH serum level could be a negative predictive marker for Axitinib effectiveness, which can aid in clinical decision making.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2023-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44067120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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