Categories of response to first line vascular endothelial growth factor receptor targeted therapy and overall survival in patients with metastatic renal cell carcinoma

Busch, Jonas; Seidel, Christoph; Goranova, Irena; Erber, Barbara; Peters, Robert W.; Friedersdorff, Frank; Magheli, Ahmed; Miller, Kurt; Grünwald, Viktor; Weikert, Steffen

doi:10.1016/j.ejca.2013.10.017

Cited by 17 publications

(10 citation statements)

References 23 publications

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“…In a recent retrospective analysis of 331 patients treated with first-line anti-VEGF therapy, only 2.7% of patients had CR as the best response, and this subgroup had median OS of 63 mo, comparing favourably with median OS of 37 mo in patients with a partial response [14]. Nevertheless, while CR is probably associated with excellent survival, most patients with long-term disease control will not experience CR [15].…”

Section: Discussionmentioning

confidence: 88%

Outcomes for Patients with Metastatic Renal Cell Carcinoma Achieving a Complete Response on Targeted Therapy: A Registry-based Analysis

et al. 2016

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Section: Discussionmentioning

confidence: 88%

Outcomes for Patients with Metastatic Renal Cell Carcinoma Achieving a Complete Response on Targeted Therapy: A Registry-based Analysis

et al. 2016

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“…[1] This data is supported by a recent analysis, which underscored the ineffectiveness of objective response (OR) to predict overall survival (OS) in mRCC treated with targeted agents. [2, 3] More surprisingly, a minority of patients who achieved a CR (2.7%) was able to attain superior OS estimates (63.2 months), indicating that deep responses may benefit clinical outcome. [2]…”

Section: Introductionmentioning

confidence: 99%

“…[2, 3] More surprisingly, a minority of patients who achieved a CR (2.7%) was able to attain superior OS estimates (63.2 months), indicating that deep responses may benefit clinical outcome. [2]…”

Section: Introductionmentioning

confidence: 99%

Depth of Remission is a Prognostic Factor for Survival in Patients with Metastatic Renal Cell Carcinoma

Grünwald¹,

McKay²,

Krajewski³

et al. 2015

European Urology

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Background Response remains an important endpoint in clinical cancer trials. However, the prognostic utility of best tumor response in metastatic renal cell carcinoma (mRCC) remains vague. Objective To define the prognostic relevance of the depth of remission in mRCC Design, setting, and participants Pooled data of 2,749 patients from phase II and III clinical trials of the Pfizer data-base in mRCC was analyzed. Tumor-shrinkage was categorized by fractions of best percent change in the sum of the largest diameter of target lesions. Outcome was computed by Kaplan-Meier curves and correlation was assessed by Cox regression, including a 6-month landmark. Intervention Sunitinib, sorafenib, axitinib, temsirolimus, temsirolimus and/or IFN-α. Outcome Measurements and Statistical Analysis Categorized tumor-shrinkage, overall survival (OS), progression free survival (PFS). Results and limitations Major tumor shrinkage of 60% or more occurred in about 10% of patients and was associated with a median overall survival (OS) of 54.5 months. With depth of remission, OS expectations declined steadily (26.4, 16.6, 10.4, and 7.3 months). The association was maintained when stratified by type of therapy, line of therapy, and performance status. The 6-month landmark Cox proportional regression analyses confirmed the prognostic relevance of major tumor shrinkage (HR 0.29; CI 95% 0.22–0.39; p<0.001). The major limitation of our study is the variability of imaging intervals among studies. Conclusions This is the first and largest analysis of best tumor response in mRCC. We demonstrate that depth of remission is an independent prognostic factor in mRCC. Patient summary It remains unknown whether tumor shrinkage during therapy is needed to achieve clinical activity in mRCC. Our analysis shows that the magnitude of tumor shrinkage correlates with a better survival in patients. This observation may be used as a clinical research tool in future trials. Trial registration NCT00054886, NCT00077974, NCT00267748, NCT00338884, NCT00137423, NCT00083889, NCT00065468, NCT00678392

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“…The heterogeneity observed in kidney tumors has been an obstacle to successful treatment and might be a major contributor to relapse 4 . Significant improvements in post-surgical treatment have been made in the last two decades: inhibitors of multiple tyrosine kinases, of mTOR or monoclonal antibodies against VEGF 5,6 . Sequential treatments with these inhibitors improve patient outcomes; nevertheless, within 2 years most tumors progress.…”

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confidence: 99%

Inhibiting WNT and NOTCH in renal cancer stem cells and the implications for human patients

et al. 2020

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Current treatments for clear cell renal cell cancer (ccRCC) are insufficient because two-thirds of patients with metastases progress within two years. Here we report the identification and characterization of a cancer stem cell (CSC) population in ccRCC. CSCs are quantitatively correlated with tumor aggressiveness and metastasis. Transcriptional profiling and single cell sequencing reveal that these CSCs exhibit an activation of WNT and NOTCH signaling. A significant obstacle to the development of rational treatments has been the discrepancy between model systems and the in vivo situation of patients. To address this, we use CSCs to establish non-adherent sphere cultures, 3D tumor organoids, and xenografts. Treatment with WNT and NOTCH inhibitors blocks the proliferation and self-renewal of CSCs in sphere cultures and organoids, and impairs tumor growth in patient-derived xenografts in mice. These findings suggest that our approach is a promising route towards the development of personalized treatments for individual patients.

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Categories of response to first line vascular endothelial growth factor receptor targeted therapy and overall survival in patients with metastatic renal cell carcinoma

Cited by 17 publications

References 23 publications

Outcomes for Patients with Metastatic Renal Cell Carcinoma Achieving a Complete Response on Targeted Therapy: A Registry-based Analysis

Outcomes for Patients with Metastatic Renal Cell Carcinoma Achieving a Complete Response on Targeted Therapy: A Registry-based Analysis

Depth of Remission is a Prognostic Factor for Survival in Patients with Metastatic Renal Cell Carcinoma

Inhibiting WNT and NOTCH in renal cancer stem cells and the implications for human patients

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