Targeted therapies for renal cell carcinoma: understanding their impact on survival

Pal, Sumanta K.; Figlin, Robert A.

doi:10.1007/s11523-010-0145-6

Cited by 16 publications

(10 citation statements)

References 45 publications

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“…While these results may represent a true discordance between PFS and OS, it is also possible that a survival benefit was obscured by the use of subsequent lines of treatment. In view of these concerns, PFS is likely to be the primary endpoint of choice in many future trials and is widely accepted as the basis for regulatory approval in RCC [16]. …”

Section: Study Endpoints and Quality Of Lifementioning

confidence: 99%

Update on targeted therapies for clear cell renal cell carcinoma

Singer

Gupta

Srinivasan

2011

Current Opinion in Oncology

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Summary VEGF and mTOR-targeted therapies continue to play a critical role in the management of advanced and metastatic RCC. Ongoing research to identify novel agents continues to build upon the work done during the elucidation of the VHL/clear cell RCC pathway. It is hoped that ongoing and planned studies will enable development of therapeutic regimens that will incorporate agents with improved toxicity and better efficacy as well as defining a role for a multidisciplinary approach to the management of advanced RCC.

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Section: Study Endpoints and Quality Of Lifementioning

confidence: 99%

Update on targeted therapies for clear cell renal cell carcinoma

Singer

Gupta

Srinivasan

2011

Current Opinion in Oncology

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“…These agents, however, only provide short-term benefit by delaying disease progression, and are not curative [6–8]. Moreover, such agents require continuous administration, exposing patients to significant side-effects [7,9]. Treatment of metastatic RCC is therefore still a therapeutic challenge in need of new options.…”

Section: Introductionmentioning

confidence: 99%

Meta-Analysis Identifies NF-κB as a Therapeutic Target in Renal Cancer

et al. 2013

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ObjectiveTo determine the expression patterns of NF-κB regulators and target genes in clear cell renal cell carcinoma (ccRCC), their correlation with von Hippel Lindau (VHL) mutational status, and their association with survival outcomes.MethodsMeta-analyses were carried out on published ccRCC gene expression datasets by RankProd, a non-parametric statistical method. DEGs with a False Discovery Rate of < 0.05 by this method were considered significant, and intersected with a curated list of NF-κB regulators and targets to determine the nature and extent of NF-κB deregulation in ccRCC.ResultsA highly-disproportionate fraction (~40%; p < 0.001) of NF-κB regulators and target genes were found to be up-regulated in ccRCC, indicative of elevated NF-κB activity in this cancer. A subset of these genes, comprising a key NF-κB regulator (IKBKB) and established mediators of the NF-κB cell-survival and pro-inflammatory responses (MMP9, PSMB9, and SOD2), correlated with higher relative risk, poorer prognosis, and reduced overall patient survival. Surprisingly, levels of several interferon regulatory factors (IRFs) and interferon target genes were also elevated in ccRCC, indicating that an ‘interferon signature’ may represent a novel feature of this disease. Loss of VHL gene expression correlated strongly with the appearance of NF-κB- and interferon gene signatures in both familial and sporadic cases of ccRCC. As NF-κB controls expression of key interferon signaling nodes, our results suggest a causal link between VHL loss, elevated NF-κB activity, and the appearance of an interferon signature during ccRCC tumorigenesis.ConclusionsThese findings identify NF-κB and interferon signatures as clinical features of ccRCC, provide strong rationale for the incorporation of NF-κB inhibitors and/or and the exploitation of interferon signaling in the treatment of ccRCC, and supply new NF-κB targets for potential therapeutic intervention in this currently-incurable malignancy.

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“…(1) These targeted agents antagonize the vascular endothelial growth factor (VEGR) receptor signaling pathway through ligand binding (bevacizumab), tyrosine kinase inhibition (sunitinib, sorafenib, pazopanib and axitinib), or inhibition of a downstream moiety, the mammalian target of rapamycin (mTOR; temsirolimus and everolimus). These agents possess several advantages over traditional immunotherapeutic strategies, such as interferon-α (IFN-α) and interleukin-2 (IL-2).…”

Section: Introductionmentioning

confidence: 99%

Impact of age on treatment trends and clinical outcome in patients with metastatic renal cell carcinoma

Pal

Hsu

et al. 2013

Journal of Geriatric Oncology

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OBJECTIVES Clinical outcomes in older adults with metastatic renal cell carcinoma (mRCC) are poorly understood, particularly in the era of targeted therapies. We characterize survival and relevant treatment-related variables in a modern series. MATERIALS AND METHODS From an institutional database including 562 patients with RCC, a total of 219 patients with metastatic disease were identified for the current analysis. Survival was assessed in four age-based cohorts: (1) age < 55, (2) age 55–64, (3) age 65–74, and (4) age ≥ 75. The number of lines of therapy rendered was collected for each patient, and the reason for treatment discontinuation was characterized. RESULTS Of the 219 patients assessed, median age was 58 (range, 26–87), and most patients had clear cell histology (82%) and prior nephrectomy (70.9%). The majority of patients were characterized as intermediate-risk (53%) by MSKCC criteria. Median survival in patients age ≥ 75 was 12.5 months, as compared to 26.4 months for patients age < 75 (P=0.003). Patients age ≥ 75 received fewer lines of systemic therapy as compared to other age-based subsets, and more frequently discontinued therapies due to toxicity. CONCLUSIONS Older adults represent a unique subpopulation of patients with mRCC, with distinct clinical outcomes. Further research is warranted to better understand the safety and tolerability of current therapies for mRCC in this group.

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Targeted therapies for renal cell carcinoma: understanding their impact on survival

Cited by 16 publications

References 45 publications

Update on targeted therapies for clear cell renal cell carcinoma

Update on targeted therapies for clear cell renal cell carcinoma

Meta-Analysis Identifies NF-κB as a Therapeutic Target in Renal Cancer

Impact of age on treatment trends and clinical outcome in patients with metastatic renal cell carcinoma

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