Adverse renal outcomes following targeted therapies in renal cell carcinoma: a systematic review and meta-analysis
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SUBMITTER: Ren S
PROVIDER: S-EPMC11234087 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo compare the effectiveness and safety of treatments for advanced or metastatic renal cell carcinoma (amRCC) after treatment with vascular endothelial growth factor (VEGF)-targeted treatment.DesignSystematic review and network meta-analysis of randomised controlled trials (RCTs) and comparative observational studies. MEDLINE, EMBASE and Cochrane Library were searched up to January 2018.ParticipantsPeople with amRCC requiring treatment after VEGF-targeted treatment.InterventionsAxitinib, cabozantinib, everolimus, lenvatinib with everolimus, nivolumab, sorafenib and best supportive care (BSC).OutcomesPrimary outcomes were overall survival (OS) and progression-free survival (PFS); secondary outcomes were objective response rate (ORR), adverse events, and health-related quality of life (HRQoL).ResultsTwelve studies were included (n=5144): five RCTs and seven observational studies. Lenvatinib with everolimus significantly increased OS and PFS over everolimus (HR 0.61, 95% Credible Interval [95%CrI]: 0.36 to 0.96 and 0.47, 95%CrI: 0.26 to 0.77, respectively) as did cabozantinib (HR 0.66, 95%CrI: 0.53 to 0.82 and 0.51, 95%CrI: 0.41 to 0.63, respectively). This remained the case when observational evidence was included. Nivolumab also significantly improved OS versus everolimus (HR 0.74, 95%CrI: 0.57 to 0.93). OS sensitivity analysis, including observational studies, indicates everolimus being more effective than axitinib and sorafenib. However, inconsistency was identified in the OS sensitivity analysis. PFS sensitivity analysis suggests axitinib is more effective than everolimus, which may be more effective than sorafenib. The results for ORR supported the OS and PFS analyses. Nivolumab is associated with fewer grade 3 or grade 4 adverse events than lenvatinib with everolimus or cabozantinib. HRQoL could not be analysed due to differences in tools used.ConclusionsLenvatinib with everolimus, cabozantinib and nivolumab are effective in prolonging the survival for people with amRCC subsequent to VEGF-targeted treatment, but there is considerable uncertainty about how they compare to each other and how much better they are than axitinib and sorafenib.Prospero registration numberCRD42017071540.
| S-EPMC6429896 | biostudies-literature
Project description:Systematic review of literature on patient-reported voice handicap following T1 glottic squamous cell carcinoma treatment using transoral laser microsurgery or radiation therapy.PubMed, Web of Science, and Scopus (1997-2013).These data sources were searched for papers reporting Voice Handicap Index (VHI) after treatment of early glottic carcinoma. Review and reference cross-checking were performed using a priori selection criteria. Study data were abstracted and publication quality categorized independently by 2 authors. Corresponding authors were contacted to maximize data for analysis. Meta-analysis was performed only with studies that included both treatment modalities, to reduce heterogeneity and maximize rigor; random effects modeling was used to pool results.Eighteen publications were identified that reported VHI data following surgery and radiotherapy for T1 glottic carcinoma. No studies were randomized. When studies that reported multiple T-stages or systematic treatment selection bias were excluded, 8 retrospective cohort studies describing 362 patients were suitable for meta-analysis. Follow-up time (mean, 47 months; range, 1-298 mo) and extent of surgical excision varied across studies. Six studies showed no VHI difference between treatment arms; 2 favored radiotherapy over surgery (1 of which reported transmuscular cordectomy for all surgical patients); and none favored surgery. Meta-analysis showed no significant difference in posttreatment VHI between radiotherapy and surgery (mean difference, -5.52; 95% confidence interval, -11.40, 0.36; heterogeneity I (2) = 61%, P = .01).VHI scores were comparable following transoral laser microsurgery and radiation therapy for T1 glottic carcinoma in the current literature, suggesting no clinically significant difference in functional voice outcomes between treatment types.
| S-EPMC5560897 | biostudies-other
Project description:BackgroundThe risk for major adverse cardiovascular events (MACE) with targeted therapies for patients with advanced renal cell carcinoma (RCC) in real-world practice remains unclear.ObjectivesThe aim of this study was to compare the risk for MACE associated with targeted cancer therapies with that associated with cytokine treatment in patients with advanced RCC.MethodsUsing Taiwan's National Health Insurance Research Database, a retrospective nationwide cohort study was conducted involving patients with advanced RCC who had received targeted therapy (sunitinib, sorafenib, pazopanib, everolimus, or temsirolimus) or cytokine therapy (interleukin-2 or interferon gamma) from 2007 to 2018. Cox proportional hazards models were used to estimate the risk for MACE (a composite of myocardial infarction, ischemic stroke, heart failure, and cardiovascular death) in the cohort using the propensity score method of stabilized inverse probability of treatment weighting.ResultsIn this cohort of 2,785 patients with advanced RCC, 2,257 (81%) and 528 (19%) had received targeted and cytokine therapy, respectively. After stabilized inverse probability of treatment weighting, the incidence rates of MACE were 6.65 and 3.36 per 100 person-years in the targeted and cytokine therapy groups, respectively (HR: 1.80; 95% CI: 1.19-2.74). Baseline history of heart failure (HR: 3.88; 95% CI: 2.25-6.71), atrial fibrillation (HR: 3.60; 95% CI: 2.16-5.99), venous thromboembolism (HR: 2.50; 95% CI: 1.27-4.92), ischemic stroke (HR: 1.88; 95% CI: 1.14-3.11), and age ≥ 65 years (HR: 1.81; 95% CI: 1.27-2.58) were independent risk factors for targeted therapy-associated MACE.ConclusionsAmong patients with advanced RCC, the risk for MACE associated with targeted cancer therapy is higher than that associated with cytokine therapy.
| S-EPMC9270629 | biostudies-literature
Project description:Renal cell carcinoma (RCC) is one of the most life-threatening urinary malignancies displaying poor response to radiotherapy and chemotherapy. Although in the recent past there have been tremendous advancements in using targeted therapies for RCC, despite that it remains the most lethal urogenital cancer with a 5-year survival rate of roughly 76%. Timely diagnosis is still the key to prevent the progression of RCC into metastatic stages as well as to treat it. But due to the lack of definitive and specific diagnostic biomarkers for RCC and its asymptomatic nature in its early stages, it becomes very difficult to diagnose it. Reliable and distinct molecular markers can not only refine the diagnosis but also classifies the tumors into thier sub-types which can escort subsequent management and possible treatment for patients. Potential biomarkers can permit a greater degree of stratification of patients affected by RCC and help tailor novel targeted therapies. The review summarizes the most promising epigenetic [DNA methylation, microRNA (miRNA; miR), and long noncoding RNA (lncRNA)] and protein biomarkers that have been known to be specifically involved in diagnosis, cancer progression, and metastasis of RCC, thereby highlighting their utilization as non-invasive molecular markers in RCC. Also, the rationale and development of novel molecular targeted drugs and immunotherapy drugs [such as tyrosine kinase inhibitors and immune checkpoint inhibitors (ICIs)] as potential RCC therapeutics along with the proposed implication of these biomarkers in predicting response to targeted therapies will be discussed.
| S-EPMC10645469 | biostudies-literature
Project description:Targeted therapy for advanced renal cell carcinoma (RCC) has recently expanded the available treatment options for patients with these malignancies. The rapid introduction of novel treatment options into clinical practice within a relatively short time frame has created some new challenges pertaining to adverse event (AE) management in patients with advanced RCC. Accumulating safety data from the pivotal phase III clinical trials of the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab plus interferon, VEGF receptor tyrosine kinase inhibitors (sunitinib, sorafenib, and pazopanib), and mammalian target of rapamycin inhibitors (temsirolimus and everolimus) have served to characterize the toxicity profiles of these novel agents. Overall, it is evident that RCC-directed targeted therapy differs from immunotherapy and cytotoxic chemotherapy in terms of a number of unique nonhematologic AEs (some of which have not been traditionally encountered in oncology practice) and that there are distinctions within and across the various classes of agents with respect to the most prominent AEs and the risk for less common but serious complications. Although treatment-associated AEs are common, the majority of AEs reported during clinical trial experiences were grade 1 or 2 in severity and manageable with intervention in the form of supportive measures and/or dosage modification. Therefore, despite the relatively complex AE profiles of RCC-directed targeted therapy, patient education, consistent monitoring with a focus on early detection by health care providers (oncologists, general physicians, nurses), and the application of emerging AE management strategies may allow for prolonged treatment in most patients with advanced RCC.
| S-EPMC3868201 | biostudies-other
Project description:ObjectiveThe optimal sequencing of targeted therapies for metastatic renal cell carcinoma (mRCC) is unknown. Observational studies with a variety of designs have reported differing results. The objective of this study is to systematically summarize and interpret the published real-world evidence comparing sequential treatment for mRCC.MethodsA search was conducted in Medline and Embase (2009-2013), and conference proceedings from American Society of Clinical Oncology (ASCO), ASCO Genitourinary Cancers Symposium (ASCO-GU), and European Society for Medical Oncology (ESMO) (2011-2013). We systematically reviewed observational studies comparing second-line mRCC treatment with mammalian target of rapamycin inhibitors (mTORi) versus vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI). Studies were evaluated for 1) use of a retrospective cohort design after initiation of second-line therapy, 2) adjustment for patient characteristics, and 3) use of data from multiple centers. Meta-analyses were conducted for comparisons of overall survival (OS) and progression-free survival (PFS).ResultsTen studies reported OS and exhibited significant heterogeneity in estimated second-line treatment effects (I2 = 68%; P = 0.001). Four of these were adjusted, multicenter, retrospective cohort studies, and these showed no evidence of heterogeneity (I2 = 0%; P = 0.61) and a significant association between second-line mTORi (>75% everolimus) and longer OS compared to VEGF TKI (>60% sorafenib) (HR = 0.82, 95% CI: 0.68 to 0.98) in a meta-analysis. Seven studies comparing PFS showed significant heterogeneity overall and among the adjusted, multicenter, retrospective cohort studies. Real-world observational data for axitinib outcomes was limited at the time of this study.ConclusionsReal-world studies employed different designs and reported heterogeneous results comparing the effectiveness of second-line mTORi and VEGF TKI in the treatment of mRCC. Within the subset of adjusted, multicenter observational studies, second-line use of mTORi was associated with significantly prolonged survival compared with second-line use of VEGF TKI.
| S-EPMC4262396 | biostudies-literature
Project description:IntroductionNumerous therapeutic agents specifically targeting the mesenchymal-epithelial transition (MET) oncogene are being developed.ObjectiveThe aim of the current review was to systematically identify and analyze clinical trials that have evaluated MET inhibitors in various cancer types and to provide an overview of their clinical outcomes.MethodsAn electronic literature search was carried out in the PubMed and Embase databases to identify published clinical trials related to MET inhibitors. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement was followed for the systematic appraisal of the literature. Data related to clinical outcomes, including progression-free survival, overall survival, objective response rate, and overall tumor response, were extracted.ResultsIn total, 49 publications were included. Among these, 51.02% were phase II studies, 14.28% were randomized controlled trials, three were phase III studies, two were prospective observational studies, and the remainder were either phase I or Ib studies. The majority (44.89%) of articles reported the clinical outcomes of MET inhibitors, including small molecules, monoclonal antibodies, and other agents, in patients with non-small-cell lung cancer (NSCLC) harboring MET alterations. MET amplification, overexpression, and MET exon 14 skipping mutations were the major MET alteration types reported across the included studies. Clinical responses/outcomes varied considerably.ConclusionThis systematic literature review provides an overview of the literature available in Embase and PubMed regarding MET-targeted therapies. MET-selective tyrosine kinase inhibitors (TKIs) (capmatinib, tepotinib, and savolitinib) may become a new standard of care in NSCLC, specifically with MET exon 14 skipping mutations. A combination of MET TKIs with epidermal growth factor receptor (EGFR) TKIs (osimertinib + savolitinib, tepotinib + gefitinib) may be a potential solution for MET-driven EGFR TKI resistance. Further, MET alteration (MET amplification/overexpression) may be an actionable target in gastric cancer and papillary renal cell carcinoma.
| S-EPMC8942886 | biostudies-literature
Project description:Background and aimsRespiratory viral infections have been implicated in the exacerbation of immune-mediated inflammatory diseases such as inflammatory bowel disease (IBD). To understand the impact of early SARS-CoV-2 variants on the risk of adverse IBD outcomes, we aimed to perform a meta-analysis of high-quality studies.MethodsCohort studies investigating adverse IBD outcomes (IBD flares, change in disease activity, change in medication, IBD-related hospitalization, and surgery) following COVID-19 were retrieved from MEDLINE and Embase. The Risk Of Bias In Nonrandomized Studies-of Exposure tool was used to assess risk of bias. Random effects model meta-analysis was used to calculate the hazard ratio (HR) for risk of adverse outcomes. Subgroup analysis was performed to estimate risk of outcomes for ulcerative colitis and Crohn's disease patients. Metaregression was performed for sex and duration of follow-up.ResultsOf the 3119 identified studies, 5 were included in the meta-analysis. A total of 34,977 IBD patients with COVID-19 and 53,270 IBD patients without recorded COVID-19 infection were identified. Two of the studies showed a high risk of bias. The random effects model did not show a statistically significant increase in the risk of adverse IBD outcomes following COVID infection (HR:1.05 [0.75-1.46]). There was no significant difference in adverse outcomes between Crohn's disease (HR: 0.91 [0.82-1.02]) and ulcerative colitis patients (HR: 0.83 [0.76-0.90]). Neither the proportion of male participants nor the mean duration of follow-up were found to be significant predictors of effect size.ConclusionIn this systematic review and meta-analysis, we find that COVID-19 did not increase the risk of adverse IBD outcomes.
| S-EPMC11803825 | biostudies-literature
Project description:The treatment of advanced and metastatic kidney cancer has been revolutionized by the development of targeted systemic therapies. Despite the growing number of available agents approved for use against clear cell renal cell carcinoma, patients with non-clear histologies, constituting approximately 1 in 4 cases of kidney cancer, have not received the same attention. The majority of clinical trials testing novel targeted therapies have excluded non-clear subtypes, providing limited therapeutic options for patients with these diagnoses and their oncologists. This review will focus on the use of targeted therapies against the non-clear histologic subtypes of renal cell carcinoma: papillary I and II, chromophobe, and collecting duct. The unique genetic and molecular profiles of each distinct non-clear kidney cancer subtype will be described, as these differences are integral to the development and effectiveness of the novel agents used to treat them. Trials focusing on non-clear kidney cancer, or those that treated clear cell tumors along with significant numbers of non-clear subtypes, will be discussed. The role of cytoreductive nephrectomy and the use of neoadjuvant and adjuvant targeted therapy will be reviewed. Lastly, areas of future research will be highlighted.
| S-EPMC3003336 | biostudies-other
Project description:IntroductionAdverse pregnancy outcomes, such as hypertensive disorders of pregnancy (HDP), gestational diabetes (GDM) and preterm birth have been linked to maternal cardiovascular disease in later life. Pre-eclampsia (PE) is associated with an increased risk of postpartum microalbuminuria, but there is no clear consensus on whether HDP increases the risk of maternal chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Similarly, it is uncertain whether GDM, preterm birth and delivery of low birth-weight infants independently predict the risk of maternal renal disease in later life. The aims of this proposed systematic review and meta-analysis are to summarise the available evidence examining the association between adverse outcomes of pregnancy (HDP, GDM, preterm birth, delivery of low birth-weight infant) and later maternal renal disease and to synthesise the results of relevant studies.Methods and analysisA systematic search of PubMed, EMBASE and Web of Science will be undertaken using a detailed prespecified search strategy. Two authors will independently review the titles and abstracts of all studies, perform data extraction and appraise the quality of included studies using a bias classification tool. Original case-control and cohort studies published in English will be considered for inclusion. Primary outcomes of interest will be CKD and ESKD; secondary outcomes will be hospitalisation for renal disease and deaths from renal disease. Meta-analyses will be performed to calculate the overall pooled estimates using the generic inverse variance method. The systematic review will follow the Meta-analyses Of Observational Studies in Epidemiology guidelines.Ethics and disseminationThis systematic review and meta-analysis will be based on published data, and thus there is no requirement for ethics approval. The results will be shared through publication in a peer reviewed journal and through presentations at academic conferences.Prospero registration numberCRD42018110891.
| S-EPMC6502020 | biostudies-literature