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Perioperative Therapy in Renal Cell Carcinoma: What Do We Know, What Have We Learned, What's Next?
1Naomi B. Haas, Abramson Cancer Center; and Robert G. Uzzo, Fox Chase Cancer Center, Philadelphia, PA.
Abstract:
Recent adjuvant vascular endothelial growth factor tyrosine kinase inhibitor trials in resected high-risk renal cell carcinoma that compared sunitinib, sorafenib, pazopanib, and axitinib with placebo controls have demonstrated mixed impact on disease-free survival, no improvement in overall survival, and, thus, controversy. Here, we discuss the results and conduct of these trials to provide new insight into the goals and strategies of treating resected renal cell cancer that is at high risk for recurrence. The potential for leveraging what we have learned from these trials to conduct successful contemporary adjuvant and perioperative immune checkpoint inhibition trials and future adjuvant trial design is discussed.
Insights
Adjuvant tyrosine kinase inhibitors in high-risk kidney cancer showed mixed disease-free survival results and no overall survival benefit, prompting a reevaluation of treatment strategies. Future trials may focus on immune checkpoint inhibitors for better outcomes.
Area of Science:
- Oncology
- Translational Research
- Clinical Trials
Background:
- Adjuvant therapy for resected high-risk renal cell carcinoma (RCC) aims to prevent recurrence.
- Vascular endothelial growth factor tyrosine kinase inhibitors (VEGF TKIs) have been investigated in this setting.
Purpose of the Study:
- To analyze the results and conduct of recent adjuvant VEGF TKI trials in high-risk resected RCC.
- To provide insights into optimizing treatment goals and strategies for high-risk RCC.
- To inform the design of future adjuvant and perioperative trials, including those with immune checkpoint inhibitors.
Main Methods:
- Review and discussion of data from adjuvant clinical trials comparing sunitinib, sorafenib, pazopanib, and axitinib against placebo in resected high-risk RCC.
- Analysis of disease-free survival (DFS) and overall survival (OS) outcomes.
- Evaluation of trial conduct and potential biases.
Main Results:
- Adjuvant VEGF TKI trials demonstrated a mixed impact on disease-free survival.
- No significant improvement in overall survival was observed across these trials.
- The findings have generated controversy regarding the efficacy of VEGF TKIs in the adjuvant setting for RCC.
Conclusions:
- Current adjuvant VEGF TKI therapy offers limited benefit for high-risk resected renal cell carcinoma.
- Lessons learned from these trials are crucial for designing more effective future adjuvant and perioperative treatment strategies.
- Immune checkpoint inhibitors represent a promising avenue for future adjuvant trials in high-risk RCC.