Jason R. Brown, Adam C. Calaway, Erik Castle, J. García, P. Barata
Background: Metastatic and unresectable non-clear cell renal cell carcinoma comprises more than a quarter of kidney cancers but does not have standardized treatment. Non-clear renal carcinoma consists of a variety of diverse histologic subtypes, including papillary, chromophobe, collecting duct, translocation, and medullary histologies, many of which carry a poor prognosis. Many prospective clinical trials exclude these kidney cancers, and for most clinical trials of non-clear cell renal cell carcinoma, only a small number of patients are enrolled. Objective: To perform a systematic review of recently published and currently enrolling prospective clinical trials for advanced non-clear cell renal cell carcinoma. Methods: A systematic search of Pubmed and MEDLINE (Ovid) was conducted as per PRISMA guidelines to identify recent prospective clinical trials in non-clear cell renal cell carcinoma. To ensure a thorough search, terms not only included non-clear cell renal carcinoma but also molecular subtypes. A review of currently enrolling clinical trials was conducted on Clinicaltrials.gov and the EU Clinical Trials Register as well. Results: A total of 33 prospective clinical trials with published results and 10 currently enrolling clinicals trials were identified. About half (48.5%) of these studies were reported in 2020 or 2021, and 36.4% were in the first-line setting. Treatments investigated in these trials included mTOR inhibitors, VEGF- and MET-targeted tyrosine kinase inhibitors, immune checkpoint inhibitors, and combinatorial strategies. Outcomes from these data revealed a wide range of response rate and progression free survival, favoring TKIs and immune checkpoint inhibitors -based combination regimens. Conclusions: Novel targeted therapies and immunotherapies have changed the landscape of treatment for advanced non-clear cell renal cell carcinoma. Combination regimens may provide even further clinical benefit and warrant further investigation in larger, randomized prospective clinical trials.
{"title":"Systematic Review of Treatment of Metastatic Non-Clear Cell Renal Cell Carcinoma","authors":"Jason R. Brown, Adam C. Calaway, Erik Castle, J. García, P. Barata","doi":"10.3233/kca-210005","DOIUrl":"https://doi.org/10.3233/kca-210005","url":null,"abstract":"Background: Metastatic and unresectable non-clear cell renal cell carcinoma comprises more than a quarter of kidney cancers but does not have standardized treatment. Non-clear renal carcinoma consists of a variety of diverse histologic subtypes, including papillary, chromophobe, collecting duct, translocation, and medullary histologies, many of which carry a poor prognosis. Many prospective clinical trials exclude these kidney cancers, and for most clinical trials of non-clear cell renal cell carcinoma, only a small number of patients are enrolled. Objective: To perform a systematic review of recently published and currently enrolling prospective clinical trials for advanced non-clear cell renal cell carcinoma. Methods: A systematic search of Pubmed and MEDLINE (Ovid) was conducted as per PRISMA guidelines to identify recent prospective clinical trials in non-clear cell renal cell carcinoma. To ensure a thorough search, terms not only included non-clear cell renal carcinoma but also molecular subtypes. A review of currently enrolling clinical trials was conducted on Clinicaltrials.gov and the EU Clinical Trials Register as well. Results: A total of 33 prospective clinical trials with published results and 10 currently enrolling clinicals trials were identified. About half (48.5%) of these studies were reported in 2020 or 2021, and 36.4% were in the first-line setting. Treatments investigated in these trials included mTOR inhibitors, VEGF- and MET-targeted tyrosine kinase inhibitors, immune checkpoint inhibitors, and combinatorial strategies. Outcomes from these data revealed a wide range of response rate and progression free survival, favoring TKIs and immune checkpoint inhibitors -based combination regimens. Conclusions: Novel targeted therapies and immunotherapies have changed the landscape of treatment for advanced non-clear cell renal cell carcinoma. Combination regimens may provide even further clinical benefit and warrant further investigation in larger, randomized prospective clinical trials.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42517882","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. Joshi, Ishan J. Patel, Pratiksha Kapse, Manmohan Singh
Background: Treatment of metastatic renal cell carcinoma (mRCC) using traditional schedule (TS, 4/2) of Sunitinib is associated with higher adverse effects compared to the alternate schedule (AS, 2/1 upfront or when switched from TS). Objective: This meta-analysis aims to compare the safety, efficacy, and percentage of patients requiring dose reduction or dose interruption between Asian (AP) and non-Asian population (NAP) receiving AS of sunitinib. Methods: Electronic databases (PubMed, EMBASE, Cochrane Library) were searched to identify studies published in the English language between May 2009- May 2019, which included patients (>18 years) with mRCC receiving AS of sunitinib. Data were analyzed using the random effect model and t-test. P < 0.05 was considered statistically significant. Results: Of 1922, 16 studies were included (eight AP, eight NAP). Among all grade AEs, mucositis (RR:0.22; 95% CI:0.12–0.40), cardiotoxicity (RR: 0.52; 95% CI: 0.31–0.88), nausea (RR:0.21; 95% CI: 0.10–0.44), hand-foot syndrome (RR:0.33; 95% CI:0.13–0.83), rash (RR: 0.52; 95% CI: 0.34–0.79), and aspartate transaminase (RR:0.57; 95% CI:0.33–0.98) were more common in AP. Leukopenia (RR:2.57; 95% CI:1.47–4.49), proteinemia (RR:4.45; 95% CI:2.12–9.33), and stomatitis (RR:4.33; 95% CI:2.6–7.23) occurred more commonly in NAP. Further, PFS was significantly longer in NAP, while longer OS was observed in AP (p < 0.001). Dose reduction was significantly higher in AP than NAP (52.08% vs. 40.6%, p = 0.0088). Conclusion: Safety profile of AS of sunitinib was similar with variations in the efficacy, dose reduction between AP and NAP. Sunitinib dose or schedule modification may mitigate AEs and enhance efficacy outcomes in mRCC by extending the treatment duration.
{"title":"Comparative Evaluation of Safety and Efficacy of Alternate Schedule (AS) of Sunitinib in Asian and Non-Asian Patient Population for the Treatment of Metastatic Renal Cell Cancer (mRCC): A Meta-Analysis","authors":"A. Joshi, Ishan J. Patel, Pratiksha Kapse, Manmohan Singh","doi":"10.3233/kca-210122","DOIUrl":"https://doi.org/10.3233/kca-210122","url":null,"abstract":"Background: Treatment of metastatic renal cell carcinoma (mRCC) using traditional schedule (TS, 4/2) of Sunitinib is associated with higher adverse effects compared to the alternate schedule (AS, 2/1 upfront or when switched from TS). Objective: This meta-analysis aims to compare the safety, efficacy, and percentage of patients requiring dose reduction or dose interruption between Asian (AP) and non-Asian population (NAP) receiving AS of sunitinib. Methods: Electronic databases (PubMed, EMBASE, Cochrane Library) were searched to identify studies published in the English language between May 2009- May 2019, which included patients (>18 years) with mRCC receiving AS of sunitinib. Data were analyzed using the random effect model and t-test. P < 0.05 was considered statistically significant. Results: Of 1922, 16 studies were included (eight AP, eight NAP). Among all grade AEs, mucositis (RR:0.22; 95% CI:0.12–0.40), cardiotoxicity (RR: 0.52; 95% CI: 0.31–0.88), nausea (RR:0.21; 95% CI: 0.10–0.44), hand-foot syndrome (RR:0.33; 95% CI:0.13–0.83), rash (RR: 0.52; 95% CI: 0.34–0.79), and aspartate transaminase (RR:0.57; 95% CI:0.33–0.98) were more common in AP. Leukopenia (RR:2.57; 95% CI:1.47–4.49), proteinemia (RR:4.45; 95% CI:2.12–9.33), and stomatitis (RR:4.33; 95% CI:2.6–7.23) occurred more commonly in NAP. Further, PFS was significantly longer in NAP, while longer OS was observed in AP (p < 0.001). Dose reduction was significantly higher in AP than NAP (52.08% vs. 40.6%, p = 0.0088). Conclusion: Safety profile of AS of sunitinib was similar with variations in the efficacy, dose reduction between AP and NAP. Sunitinib dose or schedule modification may mitigate AEs and enhance efficacy outcomes in mRCC by extending the treatment duration.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42619290","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}
S. Gulati, M. Previtera, M. Czyzyk-Krzeska, P. Lara
BACKGROUND: The gene that encodes BRCA1-associated protein 1 (BAP1) has been reported to be dysregulated in several human cancers such as uveal melanoma, malignant pleural mesothelioma, hepatocellular carcinoma, thymic epithelial tumors, and clear-cell renal cell carcinoma (ccRCC). The gene is located on the human chromosome 3p21.3, encoding a deubiquitinase and acts as a classic two-hit tumor suppressor gene. BAP1 predominantly resides in the nucleus, where it interacts with several chromatin-associated factors, as well as regulates calcium signaling in the cytoplasm. As newer therapies continue to evolve for the management of RCC, it is important to understand the role of BAP1 mutation as a prognostic and predictive biomarker. OBJECTIVE: We aimed to systematically evaluate the role of BAP1 mutations in patients with RCC in terms of its impact on prognosis and its role as a predictive biomarker. METHODS: Following PRISMA guidelines, we performed a systematic literature search using PubMed and Embase through March 2021. Titles and abstracts were screened to identify articles for full-text and then a descriptive review was performed. RESULTS: A total of 490 articles were initially identified. Ultimately 71 articles that met our inclusion criteria published between 2012–2021 were included in the analysis. Data were extracted and organized to reflect the role of BAP1 alterations as a marker of prognosis as well as a marker of response to treatments, such as mTOR inhibitors, VEGF tyrosine kinase inhibitors, and immune checkpoint inhibitors. CONCLUSIONS: Alterations in BAP1 appear to be uniformly associated with poor prognosis in patients with RCC. Knowledge gaps remain with regard to the predictive relevance of BAP1 alterations, especially in the context of immunotherapy. Prospective studies are required to more precisely ascertain the predictive value of BAP1 alterations in RCC.
{"title":"BRCA1-Associated Protein 1 (BAP-1) as a Prognostic and Predictive Biomarker in Clear Cell Renal Cell Carcinoma: A Systematic Review","authors":"S. Gulati, M. Previtera, M. Czyzyk-Krzeska, P. Lara","doi":"10.3233/kca-210006","DOIUrl":"https://doi.org/10.3233/kca-210006","url":null,"abstract":"BACKGROUND: The gene that encodes BRCA1-associated protein 1 (BAP1) has been reported to be dysregulated in several human cancers such as uveal melanoma, malignant pleural mesothelioma, hepatocellular carcinoma, thymic epithelial tumors, and clear-cell renal cell carcinoma (ccRCC). The gene is located on the human chromosome 3p21.3, encoding a deubiquitinase and acts as a classic two-hit tumor suppressor gene. BAP1 predominantly resides in the nucleus, where it interacts with several chromatin-associated factors, as well as regulates calcium signaling in the cytoplasm. As newer therapies continue to evolve for the management of RCC, it is important to understand the role of BAP1 mutation as a prognostic and predictive biomarker. OBJECTIVE: We aimed to systematically evaluate the role of BAP1 mutations in patients with RCC in terms of its impact on prognosis and its role as a predictive biomarker. METHODS: Following PRISMA guidelines, we performed a systematic literature search using PubMed and Embase through March 2021. Titles and abstracts were screened to identify articles for full-text and then a descriptive review was performed. RESULTS: A total of 490 articles were initially identified. Ultimately 71 articles that met our inclusion criteria published between 2012–2021 were included in the analysis. Data were extracted and organized to reflect the role of BAP1 alterations as a marker of prognosis as well as a marker of response to treatments, such as mTOR inhibitors, VEGF tyrosine kinase inhibitors, and immune checkpoint inhibitors. CONCLUSIONS: Alterations in BAP1 appear to be uniformly associated with poor prognosis in patients with RCC. Knowledge gaps remain with regard to the predictive relevance of BAP1 alterations, especially in the context of immunotherapy. Prospective studies are required to more precisely ascertain the predictive value of BAP1 alterations in RCC.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2021-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43147873","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}
The Clinical Trials Corner of Kidney Cancer highlights planned or ongoing high-impact studies in renal cell carcinoma (RCC). In this issue, we revisit the RADICAL trial, an important study evaluating the potential benefi t of Radium-223 therapy in RCC patients with bone metastases, which has recently been amended. In the future, attention to a specifi c trial, us metastases turnover in metastatic castration An Phase I trial of Radium-223 combined in
{"title":"Clinical Trials Corner: Reimagining RADICAL","authors":"M. Parikh","doi":"10.3233/kca-210002","DOIUrl":"https://doi.org/10.3233/kca-210002","url":null,"abstract":"The Clinical Trials Corner of Kidney Cancer highlights planned or ongoing high-impact studies in renal cell carcinoma (RCC). In this issue, we revisit the RADICAL trial, an important study evaluating the potential benefi t of Radium-223 therapy in RCC patients with bone metastases, which has recently been amended. In the future, attention to a specifi c trial, us metastases turnover in metastatic castration An Phase I trial of Radium-223 combined in","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2021-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47704745","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}
M. Parikh, Matthew E. Tenold, L. Qi, F. Lara, D. Robles, F. Meyers, P. Lara
Background: Although immune checkpoint inhibitor-based therapy has improved the outcomes of many patients with metastatic renal cell carcinoma (mRCC), most eventually develop disease progression. Newer agents that modulate immune response can possibly potentiate checkpoint inhibitor therapy. The ITK/ETK/BTK inhibitor ibrutinib has been reported to inhibit myeloid derived suppressor cells in preclinical models and to potentiate immunotherapy. We conducted an investigator-initiated trial of ibrutinib plus the PD1 inhibitor nivolumab in mRCC patients, particularly in those previously exposed to immune checkpoint inhibitors. Methods: Eligible patients had mRCC of any histologic subtype, completed at least one line of prior systemic therapy which could have included prior immunotherapy, and had acceptable end-organ function with ECOG performance status of 0–2. Treatment consisted of nivolumab 240 mg intravenously every 2 weeks plus ibrutinib 560 mg (dose level 0) or 420 mg (dose level -1) orally once daily. Cycle length was 28 days. Dose limiting toxicity (DLT) was defined as any Grade 3 or higher adverse event (AE) attributable to therapy. After identification of the recommended phase 2 dose (RP2D), up to 19 patients were enrolled to an expansion cohort to further evaluate toxicities and any early evidence of efficacy. The primary endpoints of the trial were establishment of RP2D and progression-free survival (PFS). Results: A total of 31 patients were enrolled, 6 to dose level 0, 7 (of which one was not evaluable for DLT) in dose level -1, and 18 in the expansion cohort. Median age was 60 years (range, 36–90), most had clear cell histology (n = 27; 87%), and most had prior immune checkpoint inhibitor therapy (n = 28; 90%). Three patients experienced one DLT each, all in dose level 0 (all Grade 3), namely elevated lipase, hypoalbuminemia, and nausea. No DLTs were seen in dose level –1 which was declared the RP2D. The most common Grade 3 or higher AEs include anemia (n = 5), lymphocyte count decrease (4), nausea (2), and hypotension (2). Of 28 patients evaluable for response, one patient (3.6%) had a complete response, 2 (7.1%) had a partial response, and 11 (39.2%) had stable disease, for an objective response rate of 10.7%(95%CI: 3.7%–27.2%) and a disease control rate of 50%(95%CI: 32.6%–67.4%). All responders had received prior immune checkpoint inhibitor therapy. Median PFS was 2.5 months (95%CI, 1.9 –4.8) while median OS was 9.1 months (95%CI, 6.6 –19.0). Conclusions: Ibrutinib at a dose of 420 mg orally once daily in combination with nivolumab 240 mg IV every 2 weeks is feasible and tolerable in mRCC patients. No unique immune-related AEs were observed. Anti-tumor activity was seen in patients previously exposed to PD-1 targeted therapy.
{"title":"Phase Ib/II trial of ibrutinib and nivolumab in patients with advanced refractory renal cell carcinoma1","authors":"M. Parikh, Matthew E. Tenold, L. Qi, F. Lara, D. Robles, F. Meyers, P. Lara","doi":"10.3233/kca-210128","DOIUrl":"https://doi.org/10.3233/kca-210128","url":null,"abstract":"Background: Although immune checkpoint inhibitor-based therapy has improved the outcomes of many patients with metastatic renal cell carcinoma (mRCC), most eventually develop disease progression. Newer agents that modulate immune response can possibly potentiate checkpoint inhibitor therapy. The ITK/ETK/BTK inhibitor ibrutinib has been reported to inhibit myeloid derived suppressor cells in preclinical models and to potentiate immunotherapy. We conducted an investigator-initiated trial of ibrutinib plus the PD1 inhibitor nivolumab in mRCC patients, particularly in those previously exposed to immune checkpoint inhibitors. Methods: Eligible patients had mRCC of any histologic subtype, completed at least one line of prior systemic therapy which could have included prior immunotherapy, and had acceptable end-organ function with ECOG performance status of 0–2. Treatment consisted of nivolumab 240 mg intravenously every 2 weeks plus ibrutinib 560 mg (dose level 0) or 420 mg (dose level -1) orally once daily. Cycle length was 28 days. Dose limiting toxicity (DLT) was defined as any Grade 3 or higher adverse event (AE) attributable to therapy. After identification of the recommended phase 2 dose (RP2D), up to 19 patients were enrolled to an expansion cohort to further evaluate toxicities and any early evidence of efficacy. The primary endpoints of the trial were establishment of RP2D and progression-free survival (PFS). Results: A total of 31 patients were enrolled, 6 to dose level 0, 7 (of which one was not evaluable for DLT) in dose level -1, and 18 in the expansion cohort. Median age was 60 years (range, 36–90), most had clear cell histology (n = 27; 87%), and most had prior immune checkpoint inhibitor therapy (n = 28; 90%). Three patients experienced one DLT each, all in dose level 0 (all Grade 3), namely elevated lipase, hypoalbuminemia, and nausea. No DLTs were seen in dose level –1 which was declared the RP2D. The most common Grade 3 or higher AEs include anemia (n = 5), lymphocyte count decrease (4), nausea (2), and hypotension (2). Of 28 patients evaluable for response, one patient (3.6%) had a complete response, 2 (7.1%) had a partial response, and 11 (39.2%) had stable disease, for an objective response rate of 10.7%(95%CI: 3.7%–27.2%) and a disease control rate of 50%(95%CI: 32.6%–67.4%). All responders had received prior immune checkpoint inhibitor therapy. Median PFS was 2.5 months (95%CI, 1.9 –4.8) while median OS was 9.1 months (95%CI, 6.6 –19.0). Conclusions: Ibrutinib at a dose of 420 mg orally once daily in combination with nivolumab 240 mg IV every 2 weeks is feasible and tolerable in mRCC patients. No unique immune-related AEs were observed. Anti-tumor activity was seen in patients previously exposed to PD-1 targeted therapy.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2021-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47048491","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}
Sarcomatoid renal cell carcinoma (sRCC) is an aggressive form of kidney cancer that is associated with poor prognosis. It can arise from any histologic type of renal cell carcinoma. The majority of cases will present with advanced or metastatic disease requiring systemic therapy. Nephrectomy is the treatment of choice in locally resectable disease. The therapeutic options for sRCC have evolved in the past decade. Cytotoxic chemotherapy and monotherapy with targeted therapy (VEGF and mTOR) have historically shown poor response rates and survival in the treatment of metastatic sRCC. The use of checkpoint inhibitors and their combination with targeted therapy against VEGF has changed the landscape and outcomes for renal cell carcinoma. Given the rarity of sRCC most of the data on treatment is from small cohorts or extrapolation from larger clinical trials. The benefit from the combination of checkpoint inhibitors and targeted therapy to VEGF has shown promise in the sRCC population in post hoc analysis of large clinical trials. Future research focusing on further characterizing the unique biologic and clinical features of sRCC is critical in advancing the knowledge and developing effective therapy to improve clinical outcomes and survival.
{"title":"Sarcomatoid Renal Cell Carcinoma: The Present and Future of Treatment Paradigms","authors":"N. Candelario, C. Geiger, T. Flaig","doi":"10.3233/kca-210126","DOIUrl":"https://doi.org/10.3233/kca-210126","url":null,"abstract":"Sarcomatoid renal cell carcinoma (sRCC) is an aggressive form of kidney cancer that is associated with poor prognosis. It can arise from any histologic type of renal cell carcinoma. The majority of cases will present with advanced or metastatic disease requiring systemic therapy. Nephrectomy is the treatment of choice in locally resectable disease. The therapeutic options for sRCC have evolved in the past decade. Cytotoxic chemotherapy and monotherapy with targeted therapy (VEGF and mTOR) have historically shown poor response rates and survival in the treatment of metastatic sRCC. The use of checkpoint inhibitors and their combination with targeted therapy against VEGF has changed the landscape and outcomes for renal cell carcinoma. Given the rarity of sRCC most of the data on treatment is from small cohorts or extrapolation from larger clinical trials. The benefit from the combination of checkpoint inhibitors and targeted therapy to VEGF has shown promise in the sRCC population in post hoc analysis of large clinical trials. Future research focusing on further characterizing the unique biologic and clinical features of sRCC is critical in advancing the knowledge and developing effective therapy to improve clinical outcomes and survival.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2021-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42581046","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}
H. Eggers, Marie Luise Tiemann, I. Peters, M. Kuczyk, V. Grünwald, P. Ivanyi
BACKGROUND: Lymphnode metastases (LMN) in metastatic renal cell carcinoma (mRCC) has been associated with an unfavourable prognosis. However, the prognostic impact of LNM in mRCC in context of other solid organ metastases and throughout subsequent therapeutic lines is not well-defined. OBJECTIVE: This retrospective single-center analysis was designed to elucidate the impact of LNM in the context of other solid organ metastases and throughout subsequent therapeutic lines. METHODS: mRCC patients (pts) at our center were analysed (observation period, 04/00-03/16). Primary endpoint was overall survival (OS) and the impact of line of therapy as a co-variate. Pts were grouped into: with LNM [LNM(+)], without LNM [LNN(–)]. Subgroup analyses of LNM(+) was performed including the subgroup LNM(+) and other solid organ metastases [LNM(+) other] and LNM(+) without other solid organ metastases [LMN(+) only]. RESULTS: 383/401 mRCC pts were eligible. 318 (83.2%), 230 (60.1%) and 154 (40.5%) pts received 1stL, 2ndL and 3rdL medical treatment, respectively. In the overall population OS was 40.1 months (95%CI: 32.7–47.4), with superior OS in LNM(–) compared to LNM(+) pts (log rank, HR 1.7, 95%-CI 1.3-2.2, p < 0.001). This effect was maintained across lines of therapies. LNM(+) only had a similar risk of death as LNM(–) pts (HR 1.2, 95%-CI 0.8–2.0, p = 0.4), while the risk of death was significantly increased for LNM(+) other compared to LNM(–) (HR 1.9, 95%-CI 1.5–2.6, p < 0.001). CONCLUSION: LNM(+) in mRCC is associated with a poor OS. However, impaired OS in LNM(+) might be associated with the presence of other solid organ metastases rather than with the existence of LNM alone. Further studies are warranted to support this hypothesis.
背景:转移性肾细胞癌(mRCC)的淋巴结转移(LMN)与不良预后相关。然而，在其他实体器官转移的背景下，LNM对mRCC的预后影响以及随后的治疗方案尚不明确。目的:本回顾性单中心分析旨在阐明LNM在其他实体器官转移和整个后续治疗线中的影响。方法:对我中心mRCC患者(pts)进行分析(观察期:04/00-03/16)。主要终点是总生存期(OS)和作为协变量的治疗方案的影响。患者分为:有LNM [LNM(+)]，无LNM [LNN(-)]。对LNM(+)进行亚组分析，包括LNM(+)和其他实体器官转移亚组[LNM(+)其他]和LNM(+)无其他实体器官转移亚组[LMN(+)]。结果:383/401例mRCC患者符合条件。分别有318例(83.2%)、230例(60.1%)和154例(40.5%)患者接受了1级、2级和3级药物治疗。总体生存期为40.1个月(95%CI: 32.7-47.4)， LNM(-)患者的生存期优于LNM(+)患者(log rank, HR 1.7, 95%CI 1.3-2.2, p < 0.001)。这种效果在不同的治疗方法中都得到了维持。LNM(+)组的死亡风险与LNM(-)组相似(HR 1.2, 95%-CI 0.8-2.0, p = 0.4)，而LNM(+)组的死亡风险明显高于LNM(-)组(HR 1.9, 95%-CI 1.5-2.6, p < 0.001)。结论:mRCC的LNM(+)与不良的OS相关。然而，LNM(+)的OS受损可能与其他实体器官转移的存在有关，而不仅仅是LNM的存在。进一步的研究有理由支持这一假设。
{"title":"Prognostic Impact of Lymphnode Metastases in Patients with Metastatic Renal Cell Carcinoma","authors":"H. Eggers, Marie Luise Tiemann, I. Peters, M. Kuczyk, V. Grünwald, P. Ivanyi","doi":"10.3233/kca-210129","DOIUrl":"https://doi.org/10.3233/kca-210129","url":null,"abstract":"BACKGROUND: Lymphnode metastases (LMN) in metastatic renal cell carcinoma (mRCC) has been associated with an unfavourable prognosis. However, the prognostic impact of LNM in mRCC in context of other solid organ metastases and throughout subsequent therapeutic lines is not well-defined. OBJECTIVE: This retrospective single-center analysis was designed to elucidate the impact of LNM in the context of other solid organ metastases and throughout subsequent therapeutic lines. METHODS: mRCC patients (pts) at our center were analysed (observation period, 04/00-03/16). Primary endpoint was overall survival (OS) and the impact of line of therapy as a co-variate. Pts were grouped into: with LNM [LNM(+)], without LNM [LNN(–)]. Subgroup analyses of LNM(+) was performed including the subgroup LNM(+) and other solid organ metastases [LNM(+) other] and LNM(+) without other solid organ metastases [LMN(+) only]. RESULTS: 383/401 mRCC pts were eligible. 318 (83.2%), 230 (60.1%) and 154 (40.5%) pts received 1stL, 2ndL and 3rdL medical treatment, respectively. In the overall population OS was 40.1 months (95%CI: 32.7–47.4), with superior OS in LNM(–) compared to LNM(+) pts (log rank, HR 1.7, 95%-CI 1.3-2.2, p < 0.001). This effect was maintained across lines of therapies. LNM(+) only had a similar risk of death as LNM(–) pts (HR 1.2, 95%-CI 0.8–2.0, p = 0.4), while the risk of death was significantly increased for LNM(+) other compared to LNM(–) (HR 1.9, 95%-CI 1.5–2.6, p < 0.001). CONCLUSION: LNM(+) in mRCC is associated with a poor OS. However, impaired OS in LNM(+) might be associated with the presence of other solid organ metastases rather than with the existence of LNM alone. Further studies are warranted to support this hypothesis.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2021-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45639927","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. Vogelzang, A. Monnette, Yunfei Wang, Y. Wan, N. Robert, N. Tannir
BACKGROUND: Lenvatinib with everolimus (“Len/Eve”) is approved for advanced/metastatic RCC following one antiangiogenic therapy. OBJECTIVE: This study evaluated patient characteristics, treatment patterns and overall survival (OS) with second-line or later (2L+) Len/Eve for advanced/metastatic RCC. METHODS: A retrospective observational study was conducted using electronic health records. Adult patients who initiated 2L+ Len/Eve for advanced/metastatic RCC from May 13, 2016 to July 31, 2019 were included. Patient characteristics and treatment patterns were assessed across the overall population and by post-immuno-oncology (IO) and post-tyrosine kinase inhibitors (TKI) groups. OS was estimated from Len/Eve initiation (i.e., index date) using Kaplan-Meier. RESULTS: Among the study population (n = 152), 44.1%received 2L/3L Len/Eve and median number of prior therapies was 3 (range:1–8). Median age was 63.2 years, 78.9%were Caucasian, 73.7%were male, and 56.6%had ECOG performance status 0/1. At initial diagnosis, 65.8%had stage IV disease. At index, 53.3%had an International Metastatic RCC Database Consortium risk score of intermediate/poor, 15.1%favorable, and 31.6%missing score. Sixty-five (42.8%) received IO-based regimens and 49.3%received TKIs directly before index. Median OS from index was 13.9 (95%CI: 9.5–16.5) months and 2L/3L and 4L+ were 12.1 (95%CI: 8.4–17.0) and 14.8 (95%CI: 8.9–22.5) months, respectively. Median OS for Len/Eve post-IO and post-TKI were 13.9 (95%CI: 8.4–21.3) and 14.8 (95%CI: 7.8–16.5) months, respectively. Conclusion: This study suggested that 2L+ Len/Eve has clinical effectiveness for advanced/metastatic RCC in a US community oncology setting. Future studies are needed to confirm the association of improved survival with 2L+ Len/Eve.
{"title":"Retrospective Study of Real-World Treatment Patterns and Outcomes in Advanced/Metastatic Renal Cell Carcinoma Patients Receiving Lenvatinib/Everolimus after Heavy Pretreatment1","authors":"N. Vogelzang, A. Monnette, Yunfei Wang, Y. Wan, N. Robert, N. Tannir","doi":"10.3233/kca-210127","DOIUrl":"https://doi.org/10.3233/kca-210127","url":null,"abstract":"BACKGROUND: Lenvatinib with everolimus (“Len/Eve”) is approved for advanced/metastatic RCC following one antiangiogenic therapy. OBJECTIVE: This study evaluated patient characteristics, treatment patterns and overall survival (OS) with second-line or later (2L+) Len/Eve for advanced/metastatic RCC. METHODS: A retrospective observational study was conducted using electronic health records. Adult patients who initiated 2L+ Len/Eve for advanced/metastatic RCC from May 13, 2016 to July 31, 2019 were included. Patient characteristics and treatment patterns were assessed across the overall population and by post-immuno-oncology (IO) and post-tyrosine kinase inhibitors (TKI) groups. OS was estimated from Len/Eve initiation (i.e., index date) using Kaplan-Meier. RESULTS: Among the study population (n = 152), 44.1%received 2L/3L Len/Eve and median number of prior therapies was 3 (range:1–8). Median age was 63.2 years, 78.9%were Caucasian, 73.7%were male, and 56.6%had ECOG performance status 0/1. At initial diagnosis, 65.8%had stage IV disease. At index, 53.3%had an International Metastatic RCC Database Consortium risk score of intermediate/poor, 15.1%favorable, and 31.6%missing score. Sixty-five (42.8%) received IO-based regimens and 49.3%received TKIs directly before index. Median OS from index was 13.9 (95%CI: 9.5–16.5) months and 2L/3L and 4L+ were 12.1 (95%CI: 8.4–17.0) and 14.8 (95%CI: 8.9–22.5) months, respectively. Median OS for Len/Eve post-IO and post-TKI were 13.9 (95%CI: 8.4–21.3) and 14.8 (95%CI: 7.8–16.5) months, respectively. Conclusion: This study suggested that 2L+ Len/Eve has clinical effectiveness for advanced/metastatic RCC in a US community oncology setting. Future studies are needed to confirm the association of improved survival with 2L+ Len/Eve.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2021-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46686623","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: Contact After the First Round","authors":"M. Parikh","doi":"10.3233/kca-210001","DOIUrl":"https://doi.org/10.3233/kca-210001","url":null,"abstract":"","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2021-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/kca-210001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46421828","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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