Risk of hyperglycemia attributable to everolimus in renal cell and non–renal cell carcinoma patients: A meta-analysis.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 515-515
Author(s):  
Kevin Y Xu ◽  
Raji Shameem ◽  
Shenhong Wu
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Patients ◽  
Renal Cell ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Phase Iii ◽  
Close Monitoring ◽  
High Grade ◽  
Tumor Types

515 Background: Everolimus has been used widely in cancer patients and is associated with the development of hyperglycemia. Due to confounding factors, everolimus’ specific impact on hyperglycemia has not been well understood. We performed a meta-analysis to determine the risk of hyperglycemia attributable to everolimus in cancer patients of varying tumor types. Methods: PubMed and ASCO conference abstracts up to June 2015 were systematically searched. Eligible studies included randomized controlled trials (RCTs) in which everolimus was compared to placebo in cancer patients with or without additional cancer therapies. Heterogeneity tests were performed to examine between-study differences in hyperglycemia. The incidence and relative risk of all-grade and high-grade hyperglycemia attributable to everolimus were determined using random- or fixed-effects models. Results: A total of 7 phase III and 2 phase II RCTs with various tumors were included in our analysis. Everolimus significantly increased the risk of all-grade (RR = 2.60, 95% CI: 2.03-3.31, P < 0.001) and high-grade (RR = 3.00, 95% CI: 1.72-5.23; P < 0.001) hyperglycemia. The incidences of all-grade and high-grade hyperglycemia attributable to everolimus were 6.8% (95% CI: 3.4-13.2%) and 2.5% (95%: 1.2-4.9%) respectively. The everolimus-specific risk of all-grade hyperglycemia varied significantly with tumor types (P < 0.001), with the highest incidence seen in renal cell carcinoma (27.2%, 95% CI: 22.2-32.8%) and the lowest in breast cancer (3.3%, 95% CI: 1.3-8.2%). No significant variation was found between everolimus alone or everolimus in combination with other agents. Similar results were also found for the risk of high-grade hyperglycemia attributable to everolimus. Conclusions: The specific contribution of everolimus to both all-grade and high-grade hyperglycemia may be modified significantly by tumor types. Close monitoring should be given to patients with renal cell carcinoma.

Risk of fatigue with the targeted therapy for renal cell carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20611-e20611
Author(s):  
Bilal Iqbal ◽  
Shenhong Wu
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Fixed Effects ◽  
Meta Analysis ◽  
High Grade ◽  
Fixed Effects Model ◽  
Randomized Controlled Clinical Trials ◽  
Significant Difference

e20611 Background: Fatigue is one of the major side effects associated with targeted therapeutic agents in the treatment of renal cell carcinoma (RCC), and has negatively affected the optimal use of these drugs. Currently the risk of fatigue has not been well defined. We performed a systematic review and meta-analysis of published randomized controlled clinical trials (RCT) to determine the risk of fatigue in RCC patients treated with targeted therapy. Methods: Databases including PUBMED, Web of Science, and abstracts presented at the American Society of Clinical Oncology meetings up to October, 2012 were searched to identify relevant studies. Eligible studies included prospective RCTs in which a targeted therapy was compared to a control of non-targeted therapy (placebo or interferon) with data available. Incidences and relative risk (RR) were calculated using a random- or fixed-effects model depending on the heterogeneity of the included studies. Results: A total of 5,192 RCC patients (targeted therapy: 3023, control: 2092) from 11 RCTs were selected for analysis. The overall incidences of all-grade and high-grade (ie, grade 3 or above) fatigue were 45.4% (95% CI: 33.0-58.5%) and 7.6% (95% CI: 4.1-13.5%) respectively. The incidences varied significantly among different agents (P<0.001). In comparison with overall controls, the targeted therapy did not significantly increase the risk of all-grade (RR=1.07, 95% CI: 1.0-1.35, p=0.055) or high-grade fatigue (RR= 1.01, 95% CI: 0.68-1.50, P=0.95). However, the targeted therapy significantly increased the risk of all-grade fatigue (RR 1.60, 95% CI: 1.40-2.32; P<0.001), but not high-grade fatigue (RR 1.74, 95% CI: 0.91-3.32; P=0.095) when compared to placebo. There was no significant difference between the targeted therapy and interferon in the risk of all-grade (RR 1.02, 95% CI: 0.90-1.14; P=0.90) or high-grade fatigue (RR 0.86, 95% CI: 0.55-1.36; P=0.53). Conclusions: The targeted therapy may significantly increase the risk of fatigue in a magnitude comparable to interferon.

scholarly journals Lower circulating adiponectin is associated with higher risk of renal cell carcinoma: A meta-analysis

2020 ◽  
Vol 35 (1) ◽  
pp. 57-64
Author(s):  
Jiajie Fang ◽  
Xuanli Xu ◽  
Qiqi Mao ◽  
Yufan Ying ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Significant Heterogeneity ◽  
Healthy Controls ◽  
Fixed Effects Model ◽  
Increased Risk ◽  
Carcinoma Risk

Background: Changes in circulating adiponectin have been related to the risks of various cancers. However, the association between circulating adiponectin and the risk of renal cell carcinoma has not been fully determined. A meta-analysis was performed to evaluate the relationship between circulating adiponectin and renal cell carcinoma risk. Methods: Observational studies that evaluated the association between circulating adiponectin and renal cell carcinoma risk were identified via a systematic search of PubMed and Embase databases. The difference between circulating adiponectin in renal cell carcinoma cases and healthy controls, and the multivariable adjusted association between circulating adiponectin and renal cell carcinoma risk were evaluated. A random effects model was used if significant heterogeneity existed; otherwise a fixed effects model was applied. Results: Eight case-control studies with 2624 renal cell carcinoma cases and 2904 healthy controls were included. Pooled results showed that circulating adiponectin was significantly lower in renal cell carcinoma cases than in healthy controls (mean difference = −1.08 ug/mL; 95% confidence interval (CI) −1.62, −0.54; P < 0.001). Higher circulating adiponectin was independently associated with a significantly lowered risk of renal cell carcinoma (adjusted odds ratio for 1 SD increment of adiponectin = 0.78; 95% CI: 0.63, 0.96; P = 0.02). Subgroup analyses according to characteristics including study design, ethnics of participants, blood samples, numbers of participants, mean ages of participants, and study quality showed consistent results. Conclusions: Lower circulating adiponectin is associated with increased risk of renal cell carcinoma. The potential pathophysiological mechanisms underlying the role of circulating adiponectin in the pathogenesis of renal cell carcinoma deserve further investigation.

Predictors of successful randomized phase III studies in the treatment metastatic renal cell carcinoma: A meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17105-e17105
Author(s):  
Justin Lin ◽  
Xiaobo Zhong ◽  
Matt D. Galsky ◽  
William K. Oh ◽  
Che-Kai Tsao
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Primary Endpoint ◽  
Renal Cell ◽  
Trial Design ◽  
Meta Analysis ◽  
Clinical Trial Design ◽  
Phase Iii ◽  
Published Data

e17105 Background: The success of randomized phase III therapeutic trials (RP3TT) to reach their primary endpoint is critical given the enormous resources required to conduct such studies. In an era of accelerated therapeutic development in advanced kidney cancer, we aim to identify factors in such studies associated with a positive endpoint (PE) to better understand how to optimize trial design. Methods: Using PubMed and ClinicalTrials.gov, we identified all published RP3TT in patients with metastatic renal cell carcinoma between 1/2007-9/2019. Studies were considered PE if the primary endpoint was reached, and negative endpoint (NE) if otherwise. Studies were categorized as either first line only (FLO) or second line and beyond (SLB), with adjuvant and consolidation therapy studies excluded. We collected components of study design and baseline patient characteristics and analyzed with multivariate logistic regression to evaluate the associations between each factor and PE RP3TT. Results: Of the 65 studies evaluated, only 22 RP3TT (14 FLO, 8 SLB) were found to have published data and were included, with 14 PE and 8 NE. For all studies, those with larger enrollment size (OR = 1.008, 95% CI [1.001-1.015], p = 0.021) and clear cell requirements (OR = 0.077, 95% CI [0.007-0.901], p = 0.041) were associated with PE. After adjusting for sample size, only larger enrollment size remained significant (OR = 1.007, 95% CI [1.001-1.014], p = 0.032). Other baseline patient demographic and clinical characteristic variables were not associated with PE RP3TT. Subgroup analysis of only FLO or SLB studies also did not yield any significant associations with PE RP3TT. Conclusions: Higher enrollment size was identified as factor associated with PE in RP3TT. Incomplete trial data reporting was evident, particularly in earlier studies. Further efforts are needed to better characterize factors in order to optimize clinical trial design in this disease. [Table: see text]

Survival update from a multicenter, randomized, phase III trial of vitespen versus observation as adjuvant therapy for renal cell carcinoma in patients at high risk of recurrence

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3009-3009 ◽  
Author(s):  
C. G. Wood ◽  
P. Srivastava ◽  
L. Lacombe ◽  
A. I. Gorelov ◽  
S. Gorelov ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Statistical Analyses ◽  
Stage I ◽  
Phase Iii ◽  
Disease Stage ◽  
High Grade

3009 Background: Vitespen (formerly HSPPC-96) is a novel, autologous, heat shock protein (gp96)-peptide complex vaccine. The survival registry is investigating long-term efficacy of vitespen in renal cell carcinoma (RCC) patients at high risk for recurrence postnephrectomy. Methods: Eligible patients were enrolled and active in Antigenics’ C-100–12 phase III protocol, with a last survival status of alive at study end. Patients randomized in C-100–12 (1:1, vitespen vs. observation) had AJCC stage I (T1b), II (≥5 cm; Fuhrman grade 3/4), stage III, or stage IV (M0) RCC, ≥25% clear cells, ECOG performance score 0/1 and ≥7 g viable tumor tissue for vaccine production. The registry's primary objective is to assess OS. Registry patients are contacted every 6 (no recurrence) or 3 (upon recurrence) m, for a total of 3 y from final C-100–12 data cutoff. Results: Upon C-100–12 termination, 513 of 728 patients were eligible for follow-up. Currently, 306/513 (60%) patients are in the registry database; 207 patients are being contacted. The cohort of 306 patients is well balanced by C-100–12 randomization arm: (59.8% vitespen, 59.5% observation). Formal statistical analyses are in process. Descriptively, updated OS data show a favorable trend in the vitespen arm vs. observation in all analysis sets, especially among patients with earlier-stage disease (stage I/II high grade; n = 118) or at intermediate risk for recurrence (stage I/II high grade, III T1, T2, T3a, low grade; n = 184 ), with 13/125 (10.4%) vs. 21/115 (18.3%), and 18/184 (9.8%) vs. 33/178 (18.5%) deaths reported in the vitespen and observation arms, respectively. Conclusions: The registry provides an opportunity to confirm whether the emerging survival advantage demonstrated at the data cutoff for the C-100–12 trial improves with prolonged follow-up. Formal statistical analyses are ongoing; data available to date show continuing signals of clinical benefit associated with vitespen treatment in patients with better prognostic factors. [Table: see text]

Incidence and risk of infections in renal cell cancer (RCC) and non-RCC patients treated with everolimus and temsirolimus: A meta-analysis of randomized control trials.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 353-353 ◽  
Author(s):  
Marina Kaymakcalan ◽  
Youjin Je ◽  
Guru Sonpavde ◽  
Matt D. Galsky ◽  
Paul Linh Nguyen ◽  
...  
Keyword(s):  
Renal Cell ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Cell Cancer ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Inhibitors ◽  
Tumor Type ◽  
High Grade ◽  
Tumor Types ◽  
Phase Ii And Iii

353 Background: Everolimus and temsirolimus are mammalian target of rapamycin (mTOR) inhibitors used in a variety of malignancies including renal cell carcinoma (RCC). These targeted agents have been associated with a unique set of adverse events including infections. We performed an up-to-date meta-analysis of published clinical trials to further characterize the risk of infections in cancer patients treated with mTOR inhibitors. Methods: Pubmed and oncology conference proceedings were searched for studies from January 1966 to June 2012. Eligible studies were limited to phase II and III randomized controlled trials (RCTs) of everolimus or temsirolimus that reported on patients with cancer of any tumor type including RCC and with adequate safety profiles. Summary incidence, RR, and 95% CIs were calculated using random- or fixed-effects models based on the heterogeneity of the included studies. Results: A total of 2,990 patients from 8 RCTs were included. The incidence of all-grade infections due to mTOR inhibitor treatment was 35.7% (95% CI, 28.8-43.3) and that of high-grade infections was 4.2% (95% CI, 2.1-8.4). The relative risk of all-grade infection due to mTOR inhibitors was 1.95 (95% CI, 1.67-2.29, p<.001) and that of high-grade infection was 1.91 (95% CI, 1.09-3.35, p=.024). Subgroup analysis found no difference in the incidence or risks of infections between everolimus and temsirolimus or between different tumor types (RCC vs. non RCC). Infections included respiratory tract (38.0%), urinary tract (17.1%), skin/soft tissue (3.6%), others (2.6%), and infection/not specified (38.7%). No evidence of publication bias was observed. Conclusions: Treatment with mTOR inhibitors, everolimus and temsirolimus, is associated with a significant increase in risk of infection in RCC and non-RCC patients.

Hyponatraemia as a risk factor in renal cell carcinoma treatment with nivolumab.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14528-e14528
Author(s):  
Christian Grohe ◽  
Simon Gwynn ◽  
Richard Evans
Keyword(s):  
Renal Cell Carcinoma ◽  
Risk Factor ◽  
Cell Carcinoma ◽  
Cancer Patients ◽  
Renal Cell ◽  
Negative Impact ◽  
Correct Diagnosis ◽  
Phase Iii ◽  
Cancer Data ◽  
Diagnosis And Management

e14528 Background: In the general hospital population, the incidence of hyponatraemia is reported at varying levels up to 40%. In a retrospective analysis of 3,357 cancer patients (4,702 admissions) hyponatraemia was noted in 47%. A strong and independent association between hyponatraemia and longer length of stay with higher mortality was highlighted. The investigation, diagnosis and management of hyponatraemia is often inadequate in cancer patients. This poster offers recommendations for the improved diagnosis and management of hyponatraemia patients with renal cell carcinoma treated with nivolumab. Hyponatraemia occurs in 20% of patients with renal cell carcinoma and is associated with reduced survival. Patients with hyponatraemia before treatment had a median overall survival of 5.5 months compared with 18.6 months for those with normal sodium values. Methods: Key publications concerning the incidence, evaluation and management of hyponatraemia in patients with RCC as well as unpublished data from Phase III registration studies were reviewed and the data examined to consider impacts on current oncology practice Results: Hyponatraemia is a negative prognostic indicator in cancer. Data show that effective treatment of hyponatraemia in cancer patients reduces mortality. It has been shown in vitro that a hypotonic environment is pro-tumorigenic, whereas a slightly hypertonic environment may have a negative impact on clonogenicity. This may suggest a more complex impact on outcomes in cancer patients than simply the mortality associated with hyponatraemia. The presentation of hyponatraemia in cancer patients is complex and may be caused by the direct impacts of disease, iatrogenic factors or different treatment approaches Conclusions: Hyponatraemia is the most commonly occurring electrolyte disturbance in cancer patients, potentially representing a modifiable risk factor, with resultant impact on patient survival. The clinician should be aware of the potential for Immuno-oncology agents to precipitate hyponatraemia and consider that the correct diagnosis and management of hyponatraemia may further enhance efficacy and survival.

Tolerability of axitinib in advanced renal cell carcinoma: A meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16536-e16536
Author(s):  
Bareia Chaudhry ◽  
Shenhong Wu
Keyword(s):  
Renal Cell Carcinoma ◽  
Clinical Trials ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Single Agent ◽  
Advanced Renal Cell Carcinoma ◽  
Discontinuation Rate

e16536 Background: Axitinib has been used extensively as a single agent or in combination with immunotherapy in the treatment of advanced renal cell carcinoma. It can be often discontinued due to adverse events. A meta-analysis of clinical trials was performed to evaluate the overall tolerability of axitinib in this setting. Methods: PubMed (Up to November 2020) was searched to identify clinical trials of axitinib in advanced or metastatic renal cell carcinoma. Reported data was collected to include axitinib and control discontinuation due to adverse events. A random or fixed effects model was used to determine summary incidences, relative risks, and 95% confidence intervals depending on the heterogeneity of included studies. Results: A total of 11 studies including 4,056 patients (axitinib alone n = 1384, axitinib combination n = 987, control n = 1685) were included for analysis. The summary discontinuation rate for axitinib due to adverse events was 13.4% (95% CI; 11.7-15.2%) with 8.9% (95% CI: 5.3-14.6%) as a single agent and 26.6% (95% CI:17.8 –37.8%) in combination with other agents. In comparison with controls based on randomized controlled studies, axitinib overall has similar discontinuation rate due to adverse events (RR: 1.18, 95% CI: 0.77-1.80). However, there was a significantly higher discontinuation rate with axitinib in combination with other agents including immunotherapeutic agents PD-L1 inhibitors than control treatment (RR: 1.52, 95% CI: 1.24-1.86). Conclusions: The tolerability of axitinib may vary significantly with its use as a single agent or in combination in the treatment of advanced renal cell carcinoma. Further studies are needed to improve its tolerability as a part of combination therapy.

scholarly journals Balancing the Risk-Benefit Ratio of Immune Checkpoint Inhibitor and Anti-VEGF Combination Therapy in Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Li Tao ◽  
Huiyun Zhang ◽  
Guangyu An ◽  
Haoning Lan ◽  
Yaoqi Xu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Renal Cell Carcinoma ◽  
Combination Therapy ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Statistical Difference ◽  
Meta Analysis ◽  
High Grade ◽  
Anti Vegf

BackgroundAlthough immune checkpoint inhibitors (ICIs) combined with vascular endothelial growth factor receptor (VEGFR)-targeted therapy and sunitinib monotherapy have been widely applied to metastatic renal cell carcinoma (mRCC), effectiveness and safety data are still lacking. To optimize clinical decision-making, we conducted a systematic review and meta-analysis of published randomized clinical trials to characterize the efficacy and the risk of adverse events (AEs) in patients treated with ICIs plus anti-VEGF therapy.Materials and MethodsWe used PubMed, EMBASE, and the Cochrane Library to retrieve randomized controlled trials (RCTs) published before March 27, 2021. The efficacy outcomes were progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). The pooled risk ratio (RR) and 95% confidence intervals (CI) of AEs were calculated in the safety analysis.ResultsSix RCTs involving 4,227 patients were identified after a systematic search. For OS, ICI and anti-VEGF combination therapy decreased mortality approximately 30% in the intention-to-treat population (ITT) (hazard ratio (HR) = 0.70, 95% CI: 0.57–0.87), but there was no statistical difference in patients evaluated as “favorable” by the International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) criteria compared with monotherapy (HR = 0.90, 95% CI: 0.55–1.46, p = 0.66). In terms of PFS, the progression risk for all participants declined 35% (HR = 0.65, 95% CI: 0.50–0.83) and patients evaluated as “poor” by IMDC benefited further (HR = 0.46, 95% CI: 0.36–0.58). No evident divergence was found in age and sex subgroups. The RRs of all-grade hypertension, arthralgia, rash, proteinuria, high-grade (grades 3–5) arthralgia, and proteinuria developed after combination therapy were increased compared with sunitinib. The risk of high-grade hypertension and rash showed no statistical difference. However, the risk of hand-foot skin reaction (HFSR), stomatitis, and dysgeusia decreased in combination therapy groups.ConclusionsCompared with sunitinib, OS, PFS, and ORR were significantly improved in patients receiving ICI and anti-VEGF combination therapy at the expense of increased specific AEs. More attention should be paid to individualized application of these combination therapies to achieve the best benefit-risk ratio in the clinic.Systematic Review Registration[https://inplasy.com/] INPLASY: 202130104.

scholarly journals Accuracy of CT texture analysis for differentiating low-grade and high-grade renal cell carcinoma: systematic review and meta-analysis

BMJ Open ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. e051470
Author(s):  
Wei Yu ◽  
Gao Liang ◽  
Lichuan Zeng ◽  
Yang Yang ◽  
Yinghua Wu
Keyword(s):  
Systematic Review ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Texture Analysis ◽  
Renal Cell ◽  
Meta Analysis ◽  
Low Grade ◽  
High Grade ◽  
Ct Texture Analysis ◽  
Sensitivity Specificity

ObjectivesThis study aimed to assess the accuracy of CT texture analysis (CTTA) for differentiating low-grade and high-grade renal cell carcinoma (RCC).DesignSystematic review and meta-analysis.Data sourcesPubMed, Cochrane Library, Embase, Web of Science, OVID Medline, Science Direct and Springer were searched to identify the included studies.Eligibility criteria for including studiesClinical studies that report about the accuracy of CTTA in differentiating low-grade and high-grade RCC.MethodsMultiple databases were searched to identify studies from their inception to 20 October 2021. Two radiologists independently extracted data from the primary studies. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic OR (DOR) were calculated to assess CTTA performance. The summary receiver operating characteristic (SROC) curve was plotted, and the area under the curve (AUC) was calculated to evaluate the accuracy of CTTA in grading RCC.ResultsThis meta-analysis included 11 studies, with 1603 lesions observed in 1601 patients. Values of the pooled sensitivity, specificity, PLR, NLR, DOR were 0.79 (95% CI 0.73 to 0.84), 0.84 (95% CI 0.81 to 0.87), 5.1 (95% CI 4.0 to 6.4), 0.24 (95% CI 0.19 to 0.32) and 21 (95% CI 13 to 33), respectively. The SROC curve showed that the AUC was 0.88 (95% CI 0.84 to 0.90). Deeks’ test found no significant publication bias among the studies (p=0.42).ConclusionsThe findings of this meta-analysis suggest that CTTA has a high accuracy in differentiating low-grade and high-grade RCC. A standardised methodology and large sample-based study are necessary to certain the diagnostic accuracy of CTTA in RCC grading for clinical decision making.

scholarly journals Is there a preferred first-line therapy for metastatic renal cell carcinoma? A network meta-analysis

2021 ◽  
Vol 13 ◽  
pp. 175628722110531
Author(s):  
Carlo Cattrini ◽  
Carlo Messina ◽  
Chiara Airoldi ◽  
Sebastiano Buti ◽  
Giandomenico Roviello ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Meta Analysis ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Term Survival ◽  
First Line Therapy ◽  
First Line Treatment

Background: In recent years, new therapeutic combinations based on immunotherapy provided significant benefits as a first-line treatment for patients with advanced renal cell carcinoma (mRCC). Objective: This work aims to address the lack of head-to-head comparisons and the uncertainty of the benefit from immunotherapy-based combinations in all the International Metastatic RCC Database Consortium (IMDC) subgroups. Design, setting, and participants: A systematic review and a network meta-analysis were performed. Overall survival (OS) in the intention-to-treat (ITT) population was the primary endpoint. OS according to IMDC subgroups (favorable, intermediate, poor), PD-L1 expression, and grade ⩾3 adverse events (AEs) were secondary endpoints. A SUCRA analysis was performed. Results and limitations: Six randomized phase III trials with 5121 patients were included. There was a high likelihood (82%) that nivolumab-cabozantinib was the preferred treatment in OS. The benefit of ICI-based combinations over sunitinib was unclear in the favorable-risk subgroup. Nivolumab-ipilimumab had the best risk/benefit ratio among all the ICI-based combinations. The limitations were the lack of individual patient data; the heterogeneity of patients’ characteristics, trial designs, and follow-up times; and a limited number of studies for indirect comparisons. Conclusions: A customized approach for the first-line treatment of patients with mRCC should consider the risk/benefit profile of each treatment option, especially considering the likeliness of long-term survival finally reached in this setting.

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