The Effect of Targeted Therapy on Overall Survival in Advanced Renal Cancer: A Study of the National Surveillance Epidemiology and End Results Registry Database

Vaishampayan, Ulka N.; Vankayala, Hema; Vigneau, Fawn D.; Quarshie, William; Dickow, Brenda; Chalasani, Supraja; Schwartz, Kendra

doi:10.1016/j.clgc.2013.09.007

Cited by 62 publications

(47 citation statements)

References 19 publications

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“…We therefore postulate that a significantly larger proportion of tumors from African American patients may have a HIF-independent and VEGF-independent propensity for aggressiveness, resulting in resistance to the commonly used VEGF-targeted therapies. While our results point toward a biologic rationale for the lack of improvement in survival of African American patients since the advent of targeted therapy, 10 we recognize that there are also a host of other potential factors (eg, access to health care, time to diagnosis, and appropriate treatment) that likely contribute to the racial disparities seen in advanced ccRCC. Nonetheless, the results presented herein provide insight into the potential role that genomic variation plays in the disparity observed between races.…”

Section: Discussionmentioning

confidence: 77%

Intrinsic Genomic Differences Between African American and White Patients With Clear Cell Renal Cell Carcinoma

et al. 2016

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Importance There are well-documented racial disparities in outcomes for African American patients with clear cell renal cell carcinoma (ccRCC). Despite a dramatic improvement in overall survival in white patients since the advent of targeted therapy, survival for African Americans with advanced ccRCC has not changed. There is little known about potential racial differences in tumor biology of ccRCC. Objective To determine if there are racial differences in the somatic mutation rate and gene expression of ccRCC tumors from white and African American patients. Design, Setting, and Participants Overall, 438 patients with ccRCC were identified through The Cancer Genome Atlas (TCGA) clear cell kidney (KIRC) dataset (419 white and 19 African American patients). The GSE25540 dataset containing 135 patients (125 white and 10 African American patients) was used for validation. Tumor samples were collected from numerous cancer centers and were examined for racial differences in somatic mutation rates and RNA expression. Racial differences in somatic mutation rates and RNA expression were examined. Main outcomes and Measures The comparison of somatic mutation rates and differences in RNA expression in white and African American patients with ccRCC. Results Overall, 419 ccRCC tumor data sets from non-Hispanic white patients and 19 from non-Hispanic African American patients were identified through the publically available TCGA KIRC data set, and a validation set of 125 white and 10 African American ccRCC patient tumors was identified from the publicly available GSE25540 data set. African American patients were significantly less likely than white patients to have VHL mutations (2 of 12 [17%] vs 175 of 351 [50%], respectively; P = 04) and were enriched in the ccB molecular subtype (79% in African American vs 45% in white patients; P = 005), a molecular subtype that carries a worse prognosis. It was found that RNA expression analysis revealed relative down-regulation of hypoxia-inducible factor (HIF) and vascular endothelial growth factor (VEGF)-associated pathways in African American patients compared with white patients. Conclusions and Relevance African American patients have less frequent VHL inactivation, are enriched in the ccB molecular subtype, and have decreased up-regulation of HIF-associated gene signatures than white patients. These genomic differences would predict decreased responsiveness to VEGF-targeted therapy and are a biologically plausible contributing factor to the worse survival of African American patients with ccRCC, even in the targeted therapy era.

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Section: Discussionmentioning

confidence: 77%

Intrinsic Genomic Differences Between African American and White Patients With Clear Cell Renal Cell Carcinoma

et al. 2016

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“…For patients with advanced RCC in California, 3-year OS increased from 68.2% in 1998–2003 to 74.6% in 2004–2007 ( P <0.001) 19. A study based on the nationwide US Surveillance, Epidemiology and End Results (SEER) database showed a significant improvement in OS for advanced RCC patients treated after, compared with before, the introduction of targeted therapy (median OS: 15 vs 20 months; P =0.0006) 20. A recent report utilizing the 2000–2010 SEER research file indicated a significantly reduced risk for death (HR 0.86; P <0.01) among patients diagnosed with advanced RCC in the targeted therapy era compared with pre-targeted therapy era 29.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, differences in adaptation and clinical practice when introducing new therapies cannot be ascertained from RCTs, whereas data derived from national population-based registries have the potential to provide useful real-world insights into both of these issues. Although an increasing body of information supports that targeted therapy improves OS in real-world practice,18–20 few studies have explored this on a national level. Comprehensive national cancer and drug prescription registries in the Nordic countries cover the whole population and, hence, provide a unique opportunity for studying the prognostic impact of new cancer medications within a real-life population and form the basis of robust real-world epidemiologic research 21,22…”

Section: Introductionmentioning

confidence: 99%

Overall survival in renal cell carcinoma after introduction of targeted therapies: a Norwegian population-based study

Beisland

Johannesen

Klepp

et al. 2017

OTT

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BackgroundThis population-wide retrospective, non-interventional registry study assessed changes in overall survival (OS) and factors influencing OS in Norwegian patients with renal cell carcinoma (RCC).MethodsTwo population-wide health registries were used to identify all RCC patients with (mRCC) or without metastases diagnosed before (2002–2005) and after (2006–2008 and 2009–2011) introduction of targeted therapies. Median OS was estimated using Kaplan–Meier method. Cox proportional hazards regression modeling was used to identify prognostic factors.ResultsOverall, 5,463 patients were diagnosed with RCC during 2002–2005 (n=1,898), 2006–2008 (n=1,631), and 2009–2011 (n=1,934); of these, 1,678 (31%) had mRCC. Patients diagnosed in 2009–2011 and 2006–2008 had significant (P<0.001) improvements in OS versus those diagnosed in 2002–2005: median OS, not reached and not reached versus 82.0 months in RCC; 14.0 and 12.0 months versus 9.0 months in mRCC. Similarly, OS improvements were seen in the primary and elderly (≥75 years) mRCC populations. Median OS was comparable (12 months) between clear cell and papillary mRCC, but it was longer (24.0 months) for chromophobe mRCC. Multivariate regression analyses showed that younger age, previous nephrectomy, and 1 or more prescriptions of targeted therapy were significantly associated with longer OS in mRCC patients.ConclusionOS increased in RCC and mRCC patients in Norway between 2002 and 2011 following introduction of targeted therapies.

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“…ABDEL-RAHMAN trials [29]. Some previous SEER analyses have evaluated the survival for pre-targeted vs. targeted therapy eras of the whole RCC population [30][31][32]. However, none of them dissected the survival changes according to histology.…”

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confidence: 99%

Impact of histological subtype on outcomes of renal cell carcinoma patients

Abdel‐Rahman

2018

Journal of Drug Assessment

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Background: This study aims to tackle the impact of histological subtype on the presentation and treatment trends of renal cell carcinoma (RCC). Methods: RCC cases, diagnosed from 2001 to 2013, were assembled from the Surveillance, Epidemiology and End Results (SEER) database. The incidence of different RCC histological subtypes (clear cell, papillary, chromophobe and collecting duct) was assessed and Join-Point analysis was conducted. Relevant clinicopathological characteristics were assessed and correlated with subtypes through chi-square testing. Survival analysis was then evaluated using Kaplan-Meier analysis and multivariate analyses for factors affecting overall and cancer-specific survivals were assessed. Results: A total of 89,968 RCC patients were evaluated. The incidence of different RCC subtypes has increased during the study period. Chromophobe subtype seems to have the best overall and cancerspecific survivals, whilst collecting duct subtype has the worst outcomes (p < .0001 for all endpoints). Multivariate analysis for factors affecting overall survival among non-metastatic RCC patients showed that the following factors are associated with worse overall survival (collecting duct carcinoma histology, older age, T4 disease, N2 disease, no receipt of local treatment, black race, male gender and unmarried status) (p < .0001 for all parameters). Conclusion: This analysis suggests that the prognosis of RCC varies widely according to the histological subtype. Biology-oriented preclinical and clinical assessments of novel therapeutics are needed particularly for non-clear cell RCC.

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The Effect of Targeted Therapy on Overall Survival in Advanced Renal Cancer: A Study of the National Surveillance Epidemiology and End Results Registry Database

Cited by 62 publications

References 19 publications

Intrinsic Genomic Differences Between African American and White Patients With Clear Cell Renal Cell Carcinoma

Intrinsic Genomic Differences Between African American and White Patients With Clear Cell Renal Cell Carcinoma

Overall survival in renal cell carcinoma after introduction of targeted therapies: a Norwegian population-based study

Impact of histological subtype on outcomes of renal cell carcinoma patients

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