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Updated: Aug 25, 2025
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Determining Front-Line Therapeutic Strategy for Metastatic Clear Cell Renal Cell Carcinoma
Kevin K Zarrabi1, Oladimeji Lanade2, Daniel M Geynisman2
1Sidney Kimmel Cancer Center, Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Abstract:
The therapeutic landscape for metastatic renal cell carcinoma has rapidly evolved over the years, and we are now in an era of combination therapy strategies employing immune checkpoint blockade and anti-angiogenesis targeted therapy. Since 2018, we have gained regulatory approval for four distinct combination therapies, all with survival benefits, and with guideline recommendation for use in the front-line setting. As such, treatment selection has become increasingly complex with a myriad of treatment choices but little high-level head-to-head data to guide treatment selection. Heterogeneity in tumor biology further complicates treatment selection as tumors vary in behavior and treatment responsiveness. Ongoing development of biomarkers will certainly assist in this setting, and validation of predictive markers represents an unmet need. In their absence, we highlight features of disease and nuances to datasets from landmark prospective clinical trials to help inform treatment selection. There is growing evidence to support deferring upfront systemic therapy in some patients, with opportunities for active surveillance or metastasis-directed therapy. In others, upfront systemic therapy is warranted and necessitates thoughtful consideration of multiple clinicopathologic parameters to inform optimal patient-centered decision making.
Insights
The evolving treatment for metastatic renal cell carcinoma involves immune checkpoint blockade and anti-angiogenesis combinations. Treatment selection requires careful consideration of tumor biology and clinical data due to limited head-to-head trial evidence.
Area of Science:
- Oncology
- Immunotherapy
- Translational Medicine
Background:
- Metastatic renal cell carcinoma (mRCC) treatment has shifted towards combination therapies.
- Immune checkpoint inhibitors and anti-angiogenesis agents are key components of modern mRCC regimens.
- Four combination therapies have gained approval since 2018, offering survival benefits in the front-line setting.
Purpose of the Study:
- To address the complexity of treatment selection in mRCC.
- To provide guidance on choosing optimal therapies amidst numerous options and limited head-to-head data.
- To highlight the role of tumor biology heterogeneity and the unmet need for predictive biomarkers.
Main Methods:
- Analysis of clinical data from landmark prospective trials in mRCC.
- Review of disease features and treatment response nuances.
- Evaluation of clinicopathologic parameters for patient-centered decision-making.
Main Results:
- Treatment selection is complex due to multiple approved combination therapies.
- Tumor biology heterogeneity impacts treatment responsiveness.
- Lack of robust head-to-head data necessitates careful interpretation of existing trial results.
Conclusions:
- Deferring upfront systemic therapy with active surveillance or metastasis-directed therapy is viable for some mRCC patients.
- Upfront systemic therapy is indicated for others, requiring consideration of clinicopathologic factors.
- Development and validation of predictive biomarkers are crucial for optimizing mRCC treatment selection.
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