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A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Individualizing Systemic Therapies in First Line Treatment and beyond for Advanced Renal Cell Carcinoma
Yasir Khan1, Timothy D Slattery1, Lisa M Pickering1
1The Royal Marsden Hospital NHS Foundation Trust, Fulham Road, London SW3 6JJ, UK.
Abstract:
Therapeutic options for treating advanced renal cell cancer (RCC) are rapidly evolving. Vascular endothelial growth factor (VEGF)-directed therapy, predominantly VEGF receptor (VEGFr) tyrosine kinase inhibitors (TKIs) had been the most effective first line treatment since 2005 irrespective of International Metastatic RCC Database Consortium (IMDC) risk stratification. However, immune checkpoint inhibitors (ICI) have recently changed the treatment paradigm for advanced RCC particularly as the first-line systemic treatment modality. The combination of Ipilimumab and Nivolumab provides better disease control and long-term outcomes compared with the anti-VEGFr TKI Sunitinib for IMDC intermediate- to poor-risk patients and we now have the option of using ICI with TKI upfront for all IMDC risk groups. This poses a challenge for physicians, both to select the most suitable first line regimen and the most suitable subsequent therapy given the lack of data about sequencing in this setting. This treatment landscape is expected to become more complex with the emerging treatment options. Moreover, these therapeutic options cannot be generalized as significant variability exists between individual's disease biologies and their physiologies for handling treatment adverse effects. Notable efforts are being made to identify promising predictive biomarkers ranging from neo-antigen load to gene expression profiling. These biomarkers need prospective validation to justify their utility in clinical practice and in treatment decision making. This review article discusses various clinicopathological characteristics that should be carefully evaluated to help select appropriate treatment and discusses the current status of biomarker-based selection.
Insights
Immune checkpoint inhibitors (ICI) are transforming advanced renal cell cancer (RCC) treatment, offering improved outcomes over traditional therapies. Selecting the best treatment sequence remains challenging due to evolving options and individual patient variability.
Area of Science:
- Oncology
- Immunotherapy
- Pharmacology
Background:
- Advanced renal cell cancer (RCC) treatment has historically relied on vascular endothelial growth factor (VEGF)-directed therapies, primarily VEGF receptor (VEGFr) tyrosine kinase inhibitors (TKIs).
- Immune checkpoint inhibitors (ICIs) have recently emerged as a significant advancement, altering the first-line treatment paradigm for advanced RCC.
- The combination of Ipilimumab and Nivolumab demonstrates superior disease control and long-term outcomes compared to Sunitinib in intermediate- to poor-risk patients.
Purpose of the Study:
- To review the evolving treatment landscape for advanced renal cell cancer (RCC).
- To discuss the challenges in selecting optimal first-line and subsequent therapies in the era of immunotherapy and targeted agents.
- To explore the role of clinicopathological characteristics and emerging biomarkers in guiding treatment decisions for advanced RCC.
Main Methods:
- Literature review of recent clinical trials and guidelines in advanced renal cell cancer (RCC) treatment.
- Analysis of the efficacy and sequencing of immune checkpoint inhibitors (ICIs) and VEGF-directed therapies.
- Discussion of predictive biomarker strategies for personalized treatment selection.
Main Results:
- Immune checkpoint inhibitors (ICIs), particularly in combination, offer improved outcomes for advanced RCC compared to traditional anti-VEGFr TKIs.
- The upfront use of ICI with TKI is now an option for all International Metastatic RCC Database Consortium (IMDC) risk groups.
- Significant variability in individual patient response and tolerance necessitates personalized treatment approaches.
Conclusions:
- The treatment of advanced renal cell cancer (RCC) is rapidly evolving, with ICIs becoming a cornerstone of therapy.
- Selecting the optimal treatment regimen and sequence requires careful consideration of patient-specific factors and emerging biomarkers.
- Prospective validation of predictive biomarkers is crucial for refining clinical decision-making in advanced RCC.
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